Infliximab

Infliximab
Research indicates that small molecules are the most common and more easier form of drug
therapeutics. Small molecules are easier and more cost effective to produce. However because they
are chemically produced and are ingested through tablets, it makes it difficult for them to have a
lasting affect within the body. Researchers are looking into using biologics as an alternative form of
therapeutic for certain diseases. Biologics are naturally synthesised from various sources. It has been
known that biologics would have a longer "life expectancy" within the body because it would be
given intravenously, directly into the blood stream avoiding it from being broken down by the G1
tract which would occur with a small molecule (Bayer HealthCare, ... Show more content on
Helpwriting.net ...
This would be done by injecting the human protein or expressing in the mouse, to observe the
pathology or biomarker outcome, then administering the therapeutic. This allows the action of
dosage, pharmacokinetics, and pharmacodynamics to be observed within the model. This method is
a form of a screening cascade to observe the efficacy of the drug on a mouse model. After testing
was done it was shown that the mouse anti–TNF antibody inhibited the pathology of the collagen
arthritic mouse joints, reducing inflammation in paw swelling, characterising the desired effects of
the drug. Although human disease and animal diseases are different, for collagen arthritis in mice it
is the same. This goes to show that infliximab is an effective form of biologic therapy because its
proves to reduce symptoms associated with rheumatoid arthritis as shown in mouse models. Despite
the long time it took to develop infliximab it has proven itself
... Get more on HelpWriting.net ...

Reflection Paper In Nursing
The first patient for the day walked in at 0830. Lynn, RN went to greet M. S. and she invited me
over to take her vital signs. Lynn verbalized her focused assessment of the outpatient for me. The
patient denied any problems. Ensuring the patient's privacy and offering to apply ethyl chloride as a
topical anesthesia for the patient's comfort, Lynn then accessed the patient's port. She first drew a
syringe of blood to waste. Lynn then quickly placed the pre–labeled sample tubes as they filled with
blood into a bio–hazard bag and personally delivered the samples to the lab for priority processing.
She stated that all laboratory studies for the onocology department take highest priority by the lab.
Lynn discussed the lab results with the patient. She explained that the patient is in the Nadir of her
treatment and that is why the physician is holding her treatment. Her platelets were at 18 and she
will be receiving platelets Tuesday. Lynn, explained that it is the facility's protocol to give platelets
when the patient is at or below 20.
The morning went on in similar fashion the nurses greeting, assessing, and accessing ports for lab
samples, while I took their vitals. Then at 0930, I focused on S. G. a 64 male diagnosed by
computed tomography last September with Rectal adenocarcinoma at stage IV that had metastasized
to his liver. His vital signs were stable. Patient has no known allergies. His height 175.3 cm, his
weight 75.8 kg, and his BSA at 1.92 m2 were

A Brief Look at Antiangiogenic Therapy
Although laser photocoagulation and PDT destroy pathological vessels, they neither extenuate the
primary angiogenic stimuli nor prevent the development of new vessel. Antiangiogenic substances
are able to resolve these problems. Antiangiogenic therapy prevents recurrence of AMD by
reversing the CNV lesions. Pegaptanib (brand name: Macugen) was the first intravitreal
pharmacotherapy approved by the FDA in 2004. It binds to VEGF165 and is responsible for "blood–
retinal barrier breakdown and pathological intraocular neovascularisation", subsequently inhibiting
pathological leakage and angiogenesis. According to the results of the
VEGF Inhibition Study in Ocular Neovascularisation (VISION) trial, pegaptanib is proven to be an
effective therapy for wet AMD. However, reinjections have to be done regularly as the molecule of
pegaptanib is degraded enzymatically by intraocular nucleases. Endophtalmitis, traumatic lens
injury and retinal detachment were also observed in the patients receiving this treatment.
In 2006, FDA approved the usage of ranibizumab (brand name: Lucentis), a humanized monoclonal
antibody fragment that has a high affinity for VEGF, as a therapeutic option for wet AMD.
Ranibizumab is different from pegaptanib as it is not restricted only to binding VEGF165 isoform
but binds to all human VEGF isoform. It reduces leakage in vessels as well as decreases retinal and
choroidal neovascularisation in animal models. The findings of MARINA study demonstrated that

Case Study: Forecasting Denosumab
Forecasting Denosumab
Introduction
Denosumab is a biological product used in the treatment of osteoporosis which is the condition of
fragility in bones which have lost tissue due to lack of vitamin D or inadequate calcium. This
product is the first RANK inhibitor meaning it prohibited the activity of the protein. (Calkins
2017)The prohibiting of RANK minimizes the failure of bones. Denosumab is given out by a health
care professional who injects a dosage of 60mg after every six months. (Green 2010)
Denosumab which has a market value of about $990 for a complete six months dosage has two
brands, Prolia and Xgeva. Prolia is used in the treatment of osteoporosis and Xgeva is used in the

Immunohistochemistry: Antigen Detection in Tonsillitis...
Antigen Detection in Tonsillitis Using Immunohistochemistry
Tonsillitis can be described as the inflammation of the non–encapsulated lymphoid structures,
lingual and palatine tonsils. These lymphoid tissues are part of the immune system and are the first
line of defence against pathogens in the oral cavity. The palatine and lingual tonsils are located
underneath the stratified squamous epithelial mucosa of the tongue and oropharynx. The tonsils'
response to bacterial or viral infections of the epithelial mucosa, e.g. streptococci and the Epstein–
Barr virus (EBV), is inflammation and enlargement of the tonsils and antibody responses, largely
IgA. Symptoms of tonsillitis include Sore throat and fever.
Immunohistochemistry (IHC) is a method ... Show more content on Helpwriting.net ...
Monoclonal mouse anti–human CD68 labels human monocytes and macrophages. CD68 molecule
was present on patient intrafollicular tonsil macrophages, distinguished by the brown colour.
Monoclonal Mouse anti–human CD20 reacts with an antigen which is a very useful marker for
normal and neoplastic B cells. The B–lymphocyte antigen CD20 causes B–cells to stain brown in
the IHC practice, intrafollicular B–cell presence is most notable, however cells stained brown are
also present in the interfollicular zone.
CD3 expressed in peripheral T cells, region of brown in dark purple cells lining follicle, very faint.
diH20 acted as a negative control in the experiment, all cells, both in intrafollicular zone and in
interfollicular zone stained purple. Cells stained brown in the negative control indicate non–specific
staining.
KI–67 shows B–cell proliferation presented as pink cells, largely in the intrafollicular zone but also
in the interfollicular zone, indicative of a humoral adaptive immune response.
Tissue sample presented with large population of B cells, labelled with CD20, in follicles and
macrophages labelled with CD68 were also visible in the intrafollicular zone, both are indicative of
a humoral immune response.
1. Ramos Vara JA, Miller MA. When Tissue antigens and antibodies get along: revisiting the
technical aspects of immunohistochemsistry– the red, brown and blue technique. Vet Path. 2014;
51(1):42–87.
2. Price P.

Persuasive Essay On Animal Testing
An estimated 26 million animals are mistreated every year in the United States for scientific and
commercial testing ("Background"). Animals are used to develop medical treatments, determine
toxicity of medications, check the safety of products destined for human use, and other biomedical,
commercial, and health care uses. Research on living animals has been exercised since at least 500
BC ("Background"). Most of these animals include dogs, cats, ferrets, rabbits, pigs, sheep, monkeys,
chimpanzees, rats, mice, and birds ("Harm and Suffering"). It has caused so many animals to suffer
and die painful, slow deaths. The animals that are tested are forced to eat adverse substances, inhale
harmful toxins, and remain immobilized so they can be utilized for experimentation. Not only do
they endure painful procedures, they also suffer from mental abuse. They are locked up in scanty
cages at all hours and are neglected by their holders. Animals should have basic moral rights to
proper treatment. Another problem is the minimal protection they have with the Animal Welfare Act
("Harm and Suffering"). It allows rats, mice, and birds to be experimented on and consequently
these animals make up ninety five percent of the testing population ("Rats"). Animals testing should
not be used because it is morally wrong to harm an animal for another's benefit, animals may react
differently to certain medication and cosmetics than humans, and there are other ways to do testing
that do not include

The Localization Of Proteins Inside Cells
Introduction Microscopy is the most extensively used imaging technique to discover biological
systems, in which immunocytochemistry (ICC), the localization of proteins inside cells, and
immunohistochemistry (IHC), which discloses the distribution, profusion, and localization of
biomarkers within a tissue, can be observed directly. Immunohistochemistry (IHC) mentions to the
process of detecting antigens in cells of a tissue section by exploiting the principle of antibodies
binding specifically to antigens in biological tissues With IHC, tissues are removed from the patient
either frozen or chemically well–preserved and fixed in paraffin. Segments as thin as 4μm are sliced
from frozen or paraffin–embedded tissue and fixed onto slides in ... Show more content on
Helpwriting.net ...
The human papillomavirus (HPV) is one of the most common causes of sexually transmitted disease
in both men and women around the world, especially in developing countries, where the occurrence
of asymptomatic infection varies from 2 to 44%, depending on the population and studied region.
Most HPV infection is transient and some studies show that the majority of sexually active
individuals are exposed to and acquire infection from this virus at some phase in their lives. HPV
infection is more prevalent in young adults, at the beginning of their sexual activity, which is more
important to detect the virus at the early edge to prevent from the most damages in the later of life
that leads to less impact in the economy in their country and family too. with a subsequent decline in
the prevalence rate with increasing age, likely as a result of development of an immune response
against the virus and reduction of sexual activity. At a molecular level, HPV–positive squamous cell
carcinoma less frequently harbours gross chromosomal deletions than HPV–negative squamous cell
carcinoma, and has a unique molecular signature characterized by overexpression of the tumour
suppressor protein (p16) and infrequent TP53 mutations or EGFR amplification, these molecular
markers (p16) overexpression is of particular importance as it has emerged as robust surrogate
biomarker of HPV–related oropharyngeal squamous cell

Monoclonal Antibody ( Magic Bullets ) : A Promising...
MONOCLONAL ANTIBODY ("MAGIC BULLETS") – A PROMISING TREATMENT FOR
CANCER
ANURIMA MODI
TECHNO INDIA UNIVERSITY, KOLKATA–700091
REVIEW PAPER
ABSTRACT
Background: Monoclonal antibodies (mAb) are an old immunological tool in the field of
biotechnology, immunology, biochemistry and applied biology. The use of monoclonal antibodies
for cancer therapy is one of the most versatile, powerful and important strategies in the treatment of
cancer. Over a past couple of years, the US Food and Drug Administration has approved more than a
dozen mAb's to treat certain cancers (Brain cancer, Breast cancer ,Chronic lymphocytic leukemia,
Colorectal cancer, Head and neck cancers, Hodgkin 's lymphoma, Lung cancer, Melanoma, Non–
Hodgkin 's lymphoma, ... Show more content on Helpwriting.net ...
In the early stage of a drug discovery process, researchers may be faced with little or no structure
activity relationship (SAR) information. The process by which a new drug is brought to market
stage is referred to by a number of names most commonly as the development chain or "pipeline"
and consists of a number of distinct stages. To design a rational drug, we must firstly find out which
proteins can be the drug targets in pathogenesis.
MECHANISM OF ACTION
Monoclonal antibodies achieve their therapeutic effect through various mechanisms. They can have
direct effects in producing apoptosis or programmed cell death. They can block growth factor
receptors, effectively arresting proliferation of tumor cells. In cells that express monoclonal
antibodies, they can bring about anti–idiotype antibody formation. Indirect effects include recruiting
cells that have cytotoxicity, such as monocytes and macrophages. This type of antibody–mediated
cell kill is called antibody–dependent cell mediated cytotoxicity (ADCC). Monoclonal antibodies
also bind complement, leading to direct cell toxicity, known as complement dependent cytotoxicity
(CDC).
Antibody therapy can be used in a variety of ways to treat cancer. As described above, they may act
through ADCC or CDC. An alternative approach is to conjugate the monoclonal antibody to a toxin,
a cytotoxic agent, or a radioisotope. With

Rituximab Case Study
Various mechanisms for the action of monoclonal antibodies (mAbs) have been identified:
 Complement–directed cytotoxicity (CDC):
The mAbs bind to antigen on the cell surface and exposes their binding sites for proteins. These
proteins initiate the complement cascade and trigger the release of chemotactic factors and the
formation of the membrane attack complex, which promotes target–cell lysis. Rituximab shows this
activity.
 ADCC mediated adaptive immunity:
MAbs bind to antigen on the tumour cell surface, providing the target for Fc receptors on the surface
of natural killer (NK) cells. Cross–linking of receptors with mAbs triggers release of perforin and
granzymes from NK cell that lyse the tumour cell. Cell debris is taken up by antigen–presenting ...
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The drugs targeting on immune checkpoint have demonstrated higher response rates and prolonged
overall survival in cancer patients, as suggested by clinical cases.
PD–1 is a checkpoint protein on immune cells called T cells. It normally acts as a type of "off
switch" that helps keep the T cells from attacking other cells in the body. It does this when it
attaches to PD–L1, a protein on some normal (and cancer) cells. When PD–1 binds to PD–L1, it
basically tells the T cell to leave the other cell alone. Some cancer cells have large amounts of PD–
L1, which helps them evade immune attack. CTLA–4 is another protein on some T cells that acts as
a type of "off switch" to keep the immune system in check. These two proteins are major target for
anti–tumour mAbs under development.
Pembrolizumab: approved by EU and US in 2015 and 2014. Gives treat on melanoma. It targets on
programmed cell death 1 receptor (PD–1). PD–1 receptor protein down regulate the immune system
by preventing activation of T cells. Pembrolizumab blocks the inhibitory ligand of PD–1, reduce the
PD–1 function and therefore activates more T–cells. Research suggested that cytotoxic T–cells are
more susceptible to be inhibited by PD–1, hence TC become more activated when Pembrolizumab is

Veterinary Medicine Case Study
Introduction
Diagnosis of diseases in the veterinary field by using tissue/cell culture or antibodies, are adopted by
various techniques such as neutralization (Borchers et al., 2005; Taniguchi et al., 2000), Enzyme–
Linked Immunosorbent Assay (ELISA) (Langedijk, et al., 2001), Agar Gel Immunodiffusion
(Alvarez et al., 2010) and Complement Fixation Test (CFT) (Hartley et al., 2005; Adone et al.,
2008). In the past few years ago onwards, the veterinary diagnosticians has been incorporated new
molecular techniques such as the Polymerase Chain Reaction (PCR) and Western blot and improved
older techniques through the use of recombinant antigens, monoclonal antibodies and synthetic
peptides (Okonko et al., 2006). Nowadays, the molecular ... Show more content on Helpwriting.net
...
Molecular techniques also provide opportunities to improve antigens that are used to induce
polyclonal or monoclonal antibody production, select monoclonal antibodies that recognise specific
target epitopes and purify antisera for specific diagnostic purposes (Svobodova et al., 2013). Use of
synthetic peptides (those produced by connecting amino acids together in a specified sequence) for
use as positive controls in these assays provides an opportunity to include a specific positive control
without the risks involved in producing killed agents (Langedijk, et al., 2001). Recently, the use of
transgenic plants to express veterinary pathogen proteins has been shown to be an effective method
of producing large amounts of recombinant proteins without the use of animal–origin materials
(such as foetal bovine serum or eggs) (Khandelwal et al., 2004, 28). These techniques have been
predominantly applied to the development or improvement of ELISAs and can be used to create
highly sensitive screening assays typically designed to detect all infected animals whereas highly
specific confirmatory assays was designed to detect only infected animals and reduce the number of

Protein Therapeutic Candidates : Monoclonal Antibodies (...
1. INTRODUCTION With the increasing number of protein therapeutic candidates, especially
monoclonal antibodies (mAbs) entering various stages of development, biopharmaceutical
companies are increasingly looking at innovative solutions to deliver this pipeline. For antibody
manufacturing process development, maintaining desired quality attributes while reducing time to
market, maintaining cost effectiveness, and providing manufacturing flexibility are key issues in
today 's competitive market, where several companies are often working on therapies for similar
targets and clinical indications. Since antibody therapies may require large doses over a long period
of time, manufacturing capacity becomes an issue because the drug substance must be produced in
large quantities with cost and time efficiency to meet clinical requirements and pave the way toward
commercialization. (Li et al., 2012) Following the approval of the first monoclonal antibody product
in 1986, sales growth and approval of additional products was slow until the late 1990s when the
first chimeric monoclonal antibodies were approved. With the approval of these products, followed
by the approval of humanized and then fully human monoclonal antibodies, the rate of product
approvals and sales of monoclonal antibody products has increased dramatically so that in 2013,
global sales revenue for all monoclonal antibody products was nearly $75 billion (Bptc.com, 2016),
representing approximately half of the total sales

The History Of Immunostaining Methods
The history of immunostaining methods began when Marrack produced reagents against typhus and
cholera microorganisms, using a red stain conjugated to benzidin tetraedro (1) However, Professor
Albert H. Coons from Harvard School of Medicine first introduces immunofluorescence. Coons
initial attempts to label antibodies were unsuccessful as the labels were not visible enough under the
microscope. In the early nineteen forties Coons, Creech, Jones and Berliner succeeded in tagging
antibodies (2). These antibodies were used to detect foreign antigens in tissues. This involved using
a single fluorescein isothiocyanate (FITC)–labeled anti–pneumococcal antibody to find
pneumococcal antigens in mice injected with large numbers of pneumococci (1).
In 1959 Singer used an electron–dense protein in order to achieve ultrastructural localisation. The
protein ferritin was used to tag an antibody because fluorescein lacks electron opacity. Electron
microscopy could be used in immunohistochemistry as a result of this as the presence of iron in the
protein makes it electron–dense (1). In 1965 Sternberger used uranium to develop the first electron–
opaque heavy metal technique for ultrastructural localisation (3). Owing to the large molecular size
of ferritin, ferritin–labeled antibody penetrates tissues poorly also heavy metal labeled antibody has
provided insufficient increase in contrast at the sites of antigen–antibody reactions to be useful.
Subsequently, the introduction of enzymes as

Analysis Of Eli Lilly & Co 's Disease Essay
Eli Lilly & Co's (LLY) upcoming Fall 2016 data for Alzheimer's disease drug Solanezumab has
many investors wondering what we can expect from the Phase III readout. More generally, LLY has
reignited investor interest in the Alzheimer's treatment landscape. This week we will examine the
disease and market size, and provide a brief overview of five companies (LLY, BIIB, AXON, MRK,
and AB) with Phase III AD drugs in development. Lastly, we will raise some questions (hopefully
with your help) for a free AD expert interview hosted by Slingshot Insights. What is Alzheimer's
Disease? AD is the most common type of dementia and causes problems with memory, behavior,
and thinking. Symptoms typically worsen over time and the disease is most prevalent in the elderly.
There are currently around 5 million people in the United States with AD and the number increases
annually in tandem with the aging population. Although there are currently no treatments for
Alzheimer's, the market for drugs treating symptoms of the disease (like memory loss) is around $3
billion. This market could grow significantly if a disease–modifying treatment entered the space.
The AD Companies You Should Know Although there are an abundant number of Phase I and II
trials for AD, the number declines rapidly by Phase III. Let's overview Lilly(LLY), Biogen (BIIB),
Axovant (AXON), Merck (MRK), and AB Sciences (AB) to better understand five companies with
AD Phase III trials underway. LLY has been a hot

Understanding Pharmaceutical Properties Of C Terminal...
Question 7
To improve pharmaceutical properties.
 Deletion of C–terminal lysine residues to decrease the number of charged variants.
 N–glycosylation to decrease the number of N–glycoforms.
 Hinge region engineering to limit scrambling of disulphide bonds and formation of structural
isomers.
 Remove putative N–glycosylation sites in VH and VL to prevent forming N–glycoforms.
 Introduction cysteines residues to variable regions fro site controlled cytotoxic conjugation.
 Mutation of instable hot spots in CDRs to restore antigen binding.
 Pyroglutamylation on selected C–terminal glutamine residues to decrease charge variants.
To improve antibody functions.
 Engineering variable domain to decrease pI, decrease elimination of IgG.
 Use naked Fab region or Fab–PEG fragments instead of antibody to shorten/extend serum half–
life.
 Humanisation or de–immunisation of variable parts to decrease immunogenicity.
 Modulate Fc receptors–immune cell bindings affinity through maturation or glycol–engineering,
thus to increase complements activation, enhance ADCC efficiency, increase serum half–life and
enhance anti–inflammatory properties.
 Associate Fc region with a radioactive label, cytotoxic drug or protein to develop immune–
conjugation.
Question 8
The production of human monoclonal antibodies in transgenic mice has been made possible through
the insertion of germline human immunoglobulin gene loci into the genomes of mice. Mice have
been genetically manipulated (i.e.

Biotechnology Paper
Biotechnology Paper
Biotechnology products are the yield of engineering labors that process biological material and
agents to produce a modified biological substance. Examples of biotechnology drugs are
monoclonal antibodies and recombinant DNA. Monoclonal antibodies are important reagents in the
treatment and diagnosis of disease. They have been used for diagnosis of pregnancy, detection of
presence and concentration of drugs in the blood, histocompatibility assay, and detecting shed tumor
antigens. They are antibodies that are mass produced in a laboratory from a single clone that
recognizes only one epitope of a single antigen. Recombinant DNA is DNA that has been created
artificially and codes for a specific desired protein for ... Show more content on Helpwriting.net ...
Recombinant DNA production also requires a living organism. In 1973 Boyer and Cohen developed
a method to insert DNA from one organism into the DNA of bacteria. The first step in producing a
recombinant DNA protein is to identify what portion of host DNA codes for a desired protein. After
the DNA has been identified, the specified section of host DNA is removed and isolated using
unambiguous DNA cutting proteins. The DNA fragment is inserted into a previously opened
bacteria plasmid. The altered plasmid is inserted back into the bacteria. The plasmid replicates and
produces many copies of the exogenous gene. Finally, the bacteria are stimulated to transcript the
gene for the protein that it codes for and the protein can be harvested.
Infliximab is a monoclonal antibody produced by Centocor Inc. Infliximab is composed of human
constant and murine variable antibody regions. Infliximab is produced by a recombinant cell line
cloned from a single cell isolated by limiting diffusion and is purified by steps that inactivate and
remove viruses. Infliximab binds specifically to Tumor Necrosis Factor ƒÑ (ƒnƒvTNF ¡V ƒÑ)
ƒw TNF ¡V ƒÑ ƒnrelated biological activities include induction of inflammation factors such as
interleukins 1 and 6 (IL–1 and IL–6), enhancement of leukocyte migration by increasing endothelial
layer permeability and expression of adhesion molecules by endothelial cells and leukocytes,
activation of neutrophil and eosinophil functional

Factor For Sensory Fibers, And Semaphorin3c Essay
factor for sensory fibers, and Semaphorin3C (Sema3C) and Semaphorin3F (Sema3F) repulse
sympathetic nerve fibers [6]. Whereas the primary receptor for Sema3A is neuropilin1 (NRP1),
Sema3F has a higher binding affinity to neuropilin2 (NRP2). Sema3C binds to both NRP1 and
NRP2 [7,8]. The action of Sema3A is not limited to the nervous system as NRP1 is expressed on
endothelial cells, keratinocytes, T cells, and tumor cells in breast and prostate cancer. Sema3A
inhibits angiogenesis, migration of keratinocytes, proliferation of T cells, and migration of tumor
cells [8–11]. In addition, it was recently shown that Sema3A is involved in the entry of dendritic
cells to the lymphatic system [12]. Several studies have indicated that a reduction of Sema3A
expression is involved in the exacerbation of autoimmune diseases, such as RA and systemic lupus
erythematosus (SLE) [13,14]. NRP1 mediates signal transduction through PlexinA coreceptors [15],
which are classified into four sub–families, PlexinA1–4 [16]. The Sema3A/NRP1/PlexinA complex
regulates the actin cytoskeleton through small G–proteins, including Rac and Rho [17]. In immune
cells, the Rac family is associated with the proliferation and activation of B cells [18], and the
activation of T cells induced by dendritic cells [19]. NRP1 is also a putative marker of regulatory T
cells [20], and therefore Sema3A/NRP1/PlexinA signaling may modulate regulatory T cell
functions. Vascular endothelial growth factor165 (VEGF165), a spliced

Monoclonal Antibodies And Its Effects On Medicine
Monoclonal Antibodies Monoclonal Antibodies (mAB, moABs) are used widely for basic research
and hold a great amount of information for medicine, but what are they and how are they formed.
What is the main reason we look for monoclonal antibodies? What are its purpose for use? Studies
that show these Monoclonal antibodies changed medicine, and how it helped our patients today.
How would these monoclonal antibodies change the future in medicine and how we care for our pa–
tients. Would we be able to find a cure for HIV? The process of how we produce these Mono–
clonal Antibodies will continue to change the study of medicine and our future to find a cure. Back
in the 20th century, Paul Ehrlich and Elie Metchnikoff, decided to make and ex– ... Show more
content on Helpwriting.net ...
Which had given them the hybridoma cells which provided them with the antibodies they were
looking for to successfully complete the cycle to find an antidote for an immune dis– ease. This
mixture of B–cells and myeloma cells would have hybridoma cells and make antibod– ies to known
antigens and that were immortalized With this study, it won them both a Nobel Prize in Physiology
or Medicine in 1984. If the word Monoclonal Antibodies are to be broken down, then Mono –
means single, type of plasma cells that produce the identical antigens. It can only match up to one
type of anti– gen. Antibodies are a collation of identical proteins. Monoclonal Antibodies are used to
find an– tibodies for only one type of antigen. Without monoclonal antibodies to be cloned and
fused to– gether, the process of finding stabilizing cancer and another autoimmune disease would
have never been started. Unlike polyclonal antibodies which are used to to produced different
plasma cents and bind to a different type of epitopes. How do we prepare monoclonal antibodies
(mAB) with a type of antigens? An immune cell or a myeloma cell. These molecules can interact
with cells of immune, they are also known as proteins. These antigens have the different type of
sites were cells can react and match to the different type of antibodies. To only study and form
Monoclonal antibodies, these antibodies only can match up to one site of an antigen. The fusing of
antigens to antibodies is called epi– tope.

Cancer Immunotherapy Research Paper
This original research focuses on defining cancer immunotherapy and the different types of
immunotherapy that has received regulatory approval within the past twenty–five years. Cancer
immunotherapy also known as biotherapy is "the manipulation of the immune system, or utilization
of components of the immune system, as the cancer treatment." After a brief history of
immunotherapy and the foundation of its origin is given in the introduction Dillman goes into detail
about the different types of immunotherapies. The different types of immunotherapies include
nonspecific immune stimulants Bacillus Calmette–Guerin (BCG) and Levamisole which are drugs
used to boost the immune system in a general way. Cytokines are the messengers of the immune
system; interferon–a and interleukin–2 are cytokines used to mediate and regulate immune
responses, inflammation, and hematopoiesis which is new blood cell formation. ... Show more
content on Helpwriting.net ...
There is also the radiolabeled antibodies Y–90 ibritumomab tiuxetan and I–131 tositumomab;
nonmyeloablative allogeneic transplants with donor lymphocyte infusions; and the anti–prostate
cancer cell–based therapy sipuleucel–T. All of the treatments stated above are approved based on
anticancer activity as single agents or in combination with chemotherapy and they have treated
various B– and T–cell malignancies, and numerous solid tumors, including breast, lung, colorectal,
prostate, melanoma, kidney, glioblastoma, bladder, head and neck cancers. The monoclonal
antibody Ipilimumab is expected to receive regulatory approval also in the near future based on a
randomized trial. This source is useful because it ties in with the background information needed
about immunotherapies and it reinforces more advantages of

Rituximab Research Paper
Rituximab, better known by its trade name Rituxan®, is a monoclonal antibody medication
administered intravenously. Genentech, Inc and IDEC Pharmaceuticals manufacture Rituximab. 1,3
It is a drug used to treat several diseases including: Rheumatoid Arthritis (RA), along with other
prescribed medicines; Non–Hodgkin's Lymphoma (NHL), either alone or with other chemotherapy
medicines; Chronic Lymphocytic Leukemia (CLL), along with other chemotherapy medicines
fludarabine and cyclophosphamide; Granulomatosis with Polyangiitis (GPA); and Microscopic
Polyangiitis (MPA), along with glucocorticoids. 1,2 Cost of treatment varies on the disease.
Rituximab costs are about $ per mg/l .
Rituximab is a genetically engineered chimeric human–murine antibody. 3,4 More specifically,
Rituximab is composed of the ... Show more content on Helpwriting.net ...
4 This antigen is present on more than 90 percent of B–cell NHL. However, it is not found on
hematopoietic stem cells, normal plasma cells, pro B–cells, or other normal tissues. CD20 has other
key roles such as in the activation process for cell cycle initiation and differentiation and it is
suspected to function as a calcium ion channel as well. In RA, b–cells play an important role in the
pathogenesis and associated chronic synovitis. In RA, b–cells act on multiple sites to induce an
autoimmune inflammatory response including the production of rheumatoid factor, other
autoantibodies, antigen presentation, t–cell activation, and pro–inflammatory cytokine production.
The fab domain binds to the CD20 antigen on b lymphocytes and Fc domain recruits immune
effector function to mediate B–cell lysis in vitro. Potential mechanisms of cell lysis involve
complement–dependent cytotoxicity (CDC) and antibody–dependent cell mediated cytotoxicity
(ADCC). In addition, the antibody has been shown to induce apoptosis primarily in the DHL–4
human B–cell lymphoma

The Effect Of Tnf Monoclonal Antibody On Children And...
TNF monoclonal antibody) are becoming increasingly important risk factors, especially in the
developed world, having a weakened immune system because of long courses of medication, such
as corticosteroids, chemotherapy or tumour necrosis factor blockers (used to treat some types of
arthritis)
* Immunosuppressive therapy– being very young or very old– the immune systems of people who
are young or elderly tend to be weaker than those of healthy adults.
* Malnutrion– (Low body weight 10% or more below average) Tuberculosis is closely linked to
both overcrowding and malnutrition, making it one of the principal diseases of poverty. Those at
high risk thus include: people who inject illicit drugs, inhabitants and employees of locales where
vulnerable people gather (e.g. prisons and homeless shelters), medically underprivileged and
resource–poor communities, high–risk ethnic minorities, children in close contact with high–risk
category patients, and health care providers serving these patients. Malnutrition with a poor health
or having a poor diet due to lifestyle, drug abusers , alcoholics, those living hi poverty, the homeless
etc. are more at risk of tuberculosis.
* Poverty –TB and poverty are closely related. Malnutrition, overcrowding, poor ventilation and
sanitation factors associated with poverty increase both the risk of infection and probability of
developing clinical disease. Poverty and TB form a vicious cycle. TB decreases a person's work
capacity and adds burden of

The Storage Conditions And Maintenance
Storage conditions and maintenance:
Antibodies shelf life varies from weeks to years and hence depends largely on its storage conditions.
They must be stored at an appropriate temperature, ph and in the presence of 50% glycerol or
sucrose at –20°C in order to retain its activity and prevent aggregation [18].
Sodium Azide: Sodium Azide is an antimicrobial agent that prevents the growth of bacteria in the
serum or purified antibody. It is stored at 4°C.
Short term and long term storage: Serum can be stored at 4°C for 2–3 months at a time in the
presence of sodium azide. In the absence of sodium azide the time period changes and the serum can
be kept at –20°C in order to avoid bacterial growth. Purified antibodies that contain azide can be
stored at 4°C for 2–3 months at a time to allow for use without repeated freeze/thaw cycles. Purified
antibody aliquots can be made and stored at –20°C for long–term in serum vials.
Antibody Concentration: The concentration of antibodies plays a major role. At a low protein
concentration the antibody loses its stability thus leading to loss in proteins. Also mechanically
increasing antibody concentrations should be avoided, as this also causes protein losses. BSA can be
added to purified antibody to increase concentration and improve stability.
Freeze/Thaw Cycles: Repeated freezing and thawing exerts a significant risk to antibody stability
especially with purified antibody [18].
Monoclonal antibodies can also be stored under saturated

Why Do Antibodies Bind To Antigen
1. What portion of the antibody molecule binds to antigen?
Y shaped antibody molecule has two same antigen to antibody binding sites on each arm. Antibody
molecule binds to antigen is the variable region (V region) which includes a pair of V regions: one
heavy and one light chain.
2. Do antibodies bind to antigens covalently or non–covalently?
Antibodies bind to antigens by forming covalently disulfide bond.
3. How are monoclonal antibodies superior to anti–sera?
In anti–sera the researchers have to make the antibodies of desired specificity is to immunize the
animals with the correct antigen and then will get the anti–sera from the animals' blood. This
method required many factors to be purified such as the antigen preparation and the antisera
specificities. Therefore, the monoclonal antibodies are superior to anti–sera because this method
does not require a purified form of antigen. This method uses B cells to fuse with tumor cells to
from hybridoma which will produce antibodies for the desired specificity and the product of
antibodies are identical. ... Show more content on Helpwriting.net ...
Describe one application of monoclonal antibodies.
Monoclonal antibodies to treat disease, one application of this would be the use of the antibodies in
therapy. In this therapeutic application, the mouse monoclonal antibody for CD3 antigen on the
human T cells. The use of this was to prevent the rejection of the transplanted kidneys for patients
with T cell mediated graft rejection.
5. Which topics from the reading did you find difficult to understand? Which topics from the
reading would you like to hear more about?
Do we have to remember all the different classes and isotypes of the immunoglobulin, structures,
and their

Taking a Look at Botulism
Clostridium botulinum produces toxin called Botulism neurotoxin (BoNTs) which is responsible for
botulism. There are seven serotypes BoNTs of which only A, B and E are responsible for human
botulism. These toxins bind to presynaptic nerve terminal of neuromuscular junction thus disrupting
cellular communication resulting in muscular weakness and paralysis. Various ways were
discovered for treating botulism which involve producing murine monoclonal antibodies against
BoNTs. But if such antibodies are injected into human beings such antibodies would be detected as
foreign entities and antibodies would be produced against monoclonal antibodies. The drawbacks of
use monoclonal antibodies lead to development of antigen specific antibodies.
For generating antigen specific antibodies, human peripheral blood mononuclear cells (PBMC) were
isolated from three healthy volunteers. PBMC were then immunized with interleukins and BoNT.
Invitro immunized cells were then isolated and RNA was extracted from it. The RNA was then
reverse transcribed to form cDNA. The cDNA was then used for template for production of human
IgG Fd (consisting heavy chain variable and constant region) and light chain fragments using
specific primers. The DNA obtained by amplifying IgG Fd and light chain was digested with
respective digestion enzymes and ligated into different lambda phage and cloned. The cloned lamda
phage DNA was then separated by 0.8% Agarose Gel Electrophoresis. The purified gel fragments of

Essay On Papillomavirus
Specific Aims
Recipients of blood transfusions are potentially exposed to transmissible biologic agents that are
known or suspected to be associated with specific disorders. These agents range from major known
threats such as human immunodeficiency virus (HIV), Hepatitis C virus (HCV), and Hepatitis B
virus (HBV) to novel or emerging agents of public health concern such as Dengue and Zika viruses
or the agents causing babesiosis and malaria. Human papillomavirus (HPV) DNA has been detected
in the blood and related products including the peripheral blood mononuclear cells (PBMCs), sera,
or plasma of patients with cervical cancer or HPV–associated head and neck squamous cell
carcinoma as well as in PBMCs of "healthy" blood donors. However, ... Show more content on
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Recipients usually have certain medical conditions that their immune functions may not be optimal
during the blood transfusion. Any threats that can be resolved by a healthy individual might become
problematic for these patients. The blood safety becomes a major concern to protect them from
catching diseases from the blood products. In our preliminary studies, we have demonstrated that
intravenous infection with the papillomavirus induced tumor growth at the locally wounded skin,
anogenital, and oral mucosal sites in these two preclinical models. Transfusion with virus–
contaminated blood also induced tumors at locally wounded sites of recipients. To further delineate
the risk of blood born papillomavirus and viral DNA, we plan to define the threshold dose using a
serial of virions and viral DNA dilutions. Both immunocompetent and compromised animals of
different ages will be tested in the current study. Viral presence will be tracked with our established
virological assays. Serum samples will be collected to monitor antibody generation.
Specific Aim 2: Determine the risk of different blood products in the outcome of viral infections
Blood products contain red blood cells, white blood cells, sera, and plasma. HPV DNA has been
detected in different blood products including PBMCs, sera, and plasma of HPV–positive patients
and

Enzyme Linked Immunisirbent Assay
The major use of Enzyme Linked Immunosorbent Assay (ELISA) is to titrate antibodies against
specific antigens (Crowther, 1995). This method involves an enzyme, which reacts with a colourless
substrate to form a coloured product, is covalently linked to a specific antibody that recognises a
specific antigen. If the antigen is present, the antibody–enzyme complex will bind to it, and the
enzyme component of the antibody–enzyme complex will catalyse the reaction which results in a
coloured product (Berg et al, 2002). The presence of the coloured product indicates that an antigen
is present. The ELISA, which is rapid and convenient, can detect less than a nanogram (10–9 g) of a
protein and can be performed with either polyclonal antibodies, which are antibodies that can
recognise multiple epitopes on any one antigen or monoclonal antibodies, which are antibodies that
can only detect one epitope on the antigen (Guo et al, 2006). However, the use of monoclonal
antibodies gives more reliable and accurate results due to their specificity as monoclonal antibodies
are very effective at acting as the primary antibody in an assay, or for detecting antigens within a
tissue. Also, they will usually result in reduced background staining compared to that of polyclonal
antibodies.
Indirect ELISA and direct ELISA Different types of ELISA's have been developed with
modifications to the basic steps. The key step with the ELISA assay is the direct or indirect detection
of antigen by

Clinical Signs Of Bvdv Infection
Laboratory diagnosis The clinical signs of BVDV infection are highly variable and there are many
factors that affect severity of infection like viral strain, age of affected animals, immune status,
reproductive stage and mixed infection. Therefore, diagnosis based on history, clinical signs and
postmortem examination should be considered only as preliminary diagnosis. The accurate and
confirmatory diagnosis of BVDV infection depends only on laboratory diagnosis. 1– Virus isolation
BVDV isolation in cell culture, followed by identification, is considered as the most reliable method
for diagnosis. Many different clinical samples are suitable for BVDV isolation during the viremia
stage as nasal discharges, peripheral blood leukocytes, serum, semen, aborted fetuses and feces.
However, presence of maternal antibodies in serum and buffy coat samples from newly born
animals may neutralize the virus and decrease the sensitivity of virus isolation. Virus isolation
methods are labor intensive and may take several weeks. Furthermore, virus isolation cannot
differentiate between PI animals and transiently infected animals. The FBS used as supplement for
propagation of cell lines should be tested for BVDV contamination before usage to avoid false
positive results. Dubovi et al. 2013 stated that there are many factors that may affect the success in
BVDV isolation and discussed the misconception that BVDV isolation is the gold standard for
diagnosis. Some of those factors are variation

Panleukopenia Virus Lab Report
Introduction
Feline panleukopenia virus (FPV) belongs to the Protopavovirus genus of the Parvoviridae family of
single stranded DNA viruses (Garigliany). FPV is highly stable in the environment and endemic in
many cat populations specifically in kittens (Jakel). The replication of the parvovirus genome occurs
in the nucleus of the cell which requires the cell to be in the S–phase of the cell cycle. This is
because this genome relies on the host's cell mechanism to form intermediates of double–stranded
DNA, as a result, this limits the tropism or direction of FPV to highly dividing cells found in the
intestine, bone marrow or lymphoid tissues (Garigliany). And despite the fact that the Purkinje cells
are already in the post–mitotic development stage, viral proteins ... Show more content on
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Organ samples were collected and stored in 10% formalin, and then submitted for
immunohistochemical analysis (Garigliany). Immunohistochemical staining (IHC) is a method used
for detecting antigens such as proteins in cells of a tissue section (Vara). Two types of antibodies,
monoclonal and polyclonal, were used to detect specific antigens. A commercial mouse monoclonal
anti–parvovirus antibody and a polyclonal rabbit anti–human 〖p27〗^Kip1 antibody were used as
primary antibodies while goat anti–mouse or goat anti–rabbit serum was used as the secondary
antibody (Garigliany). The binding of these antibodies to the antigen was observed using the
peroxidase anti–peroxidase method. Diaminobenzidine was also used as the chromogen and sections
were counterstained with Mayer hematoxylin (Garigliany). Cerebellar sections of an FPV infected
cats with underdeveloped cerebellum were used as the positive control for the anti–parvovirus
immunochemistry while sections of a fetal cerebellum were used as the positive control for the anti–
〖p27〗^Kip1 immunochemistry

Beta-Galactosidase and Western Blot
Beta–Galactosidase and Western Blot 0
1. EMG 9 and EMG 26 contain strain _lac–_(I– Z+ Y+) and strain _lac –_ (I+ Z–
Y–)respectively.Three genes huddled together on the chromosome are required for two strains of
_E.coli_ to utilize lactose.Consisting of three genes, namely, _lacZ_, _lacY_ and _lacA_, the _lac_
operon orderly handles these genes to code specific enzymes necessary for the metabolism of
lactose. The genes _lacZ_, _lacY_ and _lacI_ would code for beta–galactosidase, galactosidase
permease and _lac_ repressor respectively. Regulation of _lac_ operon is also tight and the operon's
negative control is made possible by _lac_ repressor (Hill, 1996). With the presence of _lac_
repressor, _lac_ operon will be deactivated and will ... Show more content on Helpwriting.net ...
In its original state, beta–galactosidase has a molecular weight of 464 kDa. Considering that this
protein consists of four complex subunits, its exposure to the denaturing activity of sodium dodecyl
sulfate can equally divide beta–galactosidase into four parts, each of which has a molecular weight
of 116 kDa. Moreover, exposure to polycramide gel electrophoresis will result to alignment of
subunits. The subunit possessing a molecular weight of 116 kDa will be regarded as the first
molecular marker in the band (Zhang et al., 2005).
As mentioned previously, the two identified bands in the eighth and ninth lane, where EMG 9 is
cultured, have high intensity and distinction. This can be explicated by the mutated _lacI_ gene
found within this strain of _E.coli_. When this gene mutates, synthesis of _lac_ repressor will not
transpire and activation of _lac_ operon will take place. Consequently, the non–mutated _lacZ_ gene
within the EMG 9 strain will be transcribed and translated. Beta–galactosidase will become
abundant resulting to increased intensity of bands. Therefore, it can be stated that there is direct
relationship between protein abundance and intensity of the bands. Protein abundance will result to
high band intensity (Hill, 1996).
The EMG 26 strain cultured on the sixth and seventh lane is a competent producer of _lacI_ gene.
This gene produces _lac_

Cynthia Robbins-Roth and the Biotechnology Industry
Cynthia Robbins–Roth is a strategic planner and business consultant to the biotechnology industry,
named one of the Top 25 Biotech All–Stars by popular business magazine Forbes. Her book,
published in year 2000, provides a broad overview of many biotech topics and draws upon her
experience and skill as a keen businesswoman. The engaging and informative work initially details
the establishment and growth of the biotechnology industry, as well as its historical origins and
information on key players in its founding. Throughout her account of this "dynamic" industry's
early struggles, great successes, and current difficulties, Robbins–Roth presents her opinion of the
industry's current viability and hopes of the future product pipeline. Robbins–Roth predicts a
revolutionary change in health management and treatment, which combined with the growing aged
population, will produce sufficient demand to propel the biotechnology industry past the well–
established small molecule pharmaceutical companies. She asserts that the biotechnology companies
will emerge as the leaders in the world's medical research and development. Robbins–Roth further
explains the intricacies of financing a biotechnology venture, the necessity of efficient risk
management, and the difficulty of selling an idea to non–scientist investors. The author recalls that
in the nascent biotechnology industry, companies were "trying to be all things to all markets,"
developing products for nickel mining, oil

System Lupus Erythematosus Case
1) What condition is the monoclonal antibody designed to treat?
Ustekinumab is a monoclonal antibody that is designed to treat immune mediated inflammation
disoreders. Examples of these disorders are Psoriasis, Systemic Lupus Erythematosus, Ankylosing
Spondylitis, and Crohn's Disease. All these disorders are examples of inflammatory problem due to
either the over stimulation of interlukeins protein or the body sees itself as a foreign matter and it
attacks itself as the result. In the case of System Lupus Erythematosus the immune system attack
major organs in the body, making it life threating for patients.
2) What is the specific target of the Ab and how does the treatment work to control the condition?
To answer this question, we have

Useful Medicinal Compounds Derived from Animals
Tittle: Useful medicinal compounds derived from animals In modern medication, monoclonal
antibody has been used to treat various kinds of disease. For cancer therapy, monoclonal antibody is
extremely success. Monoclonal antibody, an immune protein with specific binding site and purified
from mouse, can bind with target protein (Campbell NA, 1996). Such as: Specific antigen, growth
factor and so on. As tumor cell always avoid immune system and even try to suppress the immune
response, they always avoid immune defense. However, if monoclonal antibody is presented, they
will bind with the target protein and immune system can recognize. Finally, immune response will
be triggered. Tumor cell can be killed by B–cell or Phagocyte. Over a ... Show more content on
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The immune system is a system of biological processes within an organism against the invasion
from the surrounding. And different antigen is produced by different type of gene (Campbell NA,
1996). The evolutionary principles state that within a population, there are organism with different
phenotypes and genotypes. There is a gene pool in the population and certain individuals are
selected for or against by the environment (Laurent P.A, 2010). For immune system, the B–cell
antigen can be randomly produced and it can basically recognized all pathogen even HIV. However,
as only specific antigen can be produced and useful for defense. So, not all of the organisms can
survive after infection but some can. In this process, gene that responsible for making antibodies
allows the organism to have a selective advantage over other organism (Nieri P, 2009). With natural
selection, only the one with gene against these diseases can survive and produce antibodies. They
are able to survive and that possess these genes survive till sexual maturity and they can pass their
gene to offspring (Bsargent, 2011). Lastly, evolution theory also point that genetic code is universal
and all organism come from the same origin. In other word, the organism in the earth has the same
DNA replication process, cell division. The protein synthesis and gene expression are the same in
the mice and human being. Their antibodies have a similar

Papillomavirus Infected Spermatozoa
Specific Aim 2: Evaluate the effect of neutralizing antibody treatment on papillomavirus infected
spermatozoa
Rationale: HPVs initially bind to negatively charged cell–surface glycosaminoglycans, particularly
heparin sulfate proteoglycans, on cultured epithelial cells (63–65). In mammals, both spermatozoa
and oocytes surface proteins are highly glycosylated, and these glycoproteins may attract
papillomavirus (66). Whether these bindings are reversible is unknown. Semen washing procedures
showed effective for blocking the HIV transmission (20), but they do not eliminate HPV infection
from spermatozoa in infertile patients (21). For humans, the semen and spermatozoa have been
reported positive for HPV (16–19, 49, 50, 67). Direct binding of ... Show more content on
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The blastocyst development will be evaluated and recorded with a live microscopy. The cells at
different fertilization stages will also be harvested for viral presence by Q–PCR and QRT–PCR (33).
Blastocysts formed from in vitro fertilization from MmuPV1 infected spermatozoa treated with
MPV.A4 or H11.B2 will also be implanted into surrogate female B6 mice (N=20/group).
Anticipated Results and Interpretation After the completion of the proposed experiments, we expect
to have determined whether the neutralizing antibody can reverse PV's impact on embryo
development in vitro and in vivo. Our preliminary studies have demonstrated that viral particles
bind to the surface of spermatozoa and oocytes of wild type B6 mice and impeded embryo
development in vitro. We predict that MPV.A4 will reverse the binding and subsequent hindrance of
papillomavirus on the embryo development. Our experienced team of experts will monitor
blastocyst formation daily and record the changes via a live microscopy.
Potential Pitfalls, Alternative Approaches, and Future Directions The primary challenge of this study
is that how to maintain spermatozoa and oocytes in vitro for more than 24 hours without loss of
viability. Several media have been tested in other laboratories, and we have

Difficile Infection And Prevention Case Study
Concepts
1–C. Diff produces exotoxins which are toxin A and toxin B. These toxins are the main virulence
factors and are mediated C. Difficile pathogenicity. Toxin A targets intestinal epithelial cells via
optical part of the cells and destroys tight junctions in order to gain access and spread to the
epithelial cells with toxin B. Unlike toxin A, Toxin B has a variety of tropism. There is also another
toxin called binary toxin in hypervirulent strains. It is not pathogenic. Indeed, It is increased
bacterial adherence. This strain is found more common in animals.
2– Foul smelling diarrhea is a characteristic of C. Difficile infection. When someone suspected with
difficile infection, there are many lab tests to diagnose and confirm the case. ... Show more content
on Helpwriting.net ...
Difficile infection. Currently, there are developing vaccines, toxoid–based vaccines but
seroconversion in elderly and a monoclonal antibodies vaccine but is not significant protection
against hypervirulent strains. There is a new approach to developing a vaccine which is DNA
vaccine with electroporation. Dr. Kutzler lab is an example, which uses DNA vaccine based on
CDT, TcdA, and TcdB.
Facts:
1– It is interesting to know that Fecal Microbiota Transplantation can use instead of antibiotics to
treat C. Difficile. I have never known about this approach. I'm thinking it is also helpful for patients
who are antibiotic resistance and treat other diseases associated with gut microbiota.
2– Bacteriocin seems interesting for CDI prevention. I found an article showed other molecular
functions for Bacteriocins. Bacteriocins can act as antiviral agents. For instance, Enterococcus
faecium produces Enterocin CRL 35, which can inhibit HSV–1 and HSV–2 at the late stage of
replication. In addition, Bacteriocins can act as anticancer agents by binding cationic bacteriocins to
the negatively charged cell membrane of cancer cells. For instance, Pseudomonas aeruginosa
produces bacteriocin azurin which binds to

A Note On Gs Expression System
a) GS expression system is used to select high–express cells, where glutamine synthetase (GS) is
used as a selectable marker. Normal functioned cell produce use glutamate and ammonium to
produce glutamine, with the presence of glutamine synthetase. To select, firstly, glutamine was
eliminated from culture media as the selective pressure. Only cell with strong expression potential
can overcome this condition. The cells survived this selection then proceeded to the second
selection, where methionine sulphoxamine (MSX) was added into the media. MSX is a specific
inhibitor of GS that stop normal GS function. Therefore, only cells whose plasmid contains both the
gene of interest and a copy the glutamine synthetase (GS) gene can survive this condition. Due to
the presence of GS gene in their plasmid, the glutamine synthesis was not halted in these survived
high–expresser cells. These cells were hence selected for cell–line production.
b) The specific productivity (qp) in mammalian cell bioreactor mean the amount of cells made per
unit time per volume. To increase bioreactor productivity, the value of qp need to be maximised. To
achieve a high specific productivity, a cell line with higher efficiency is needed. A well–designed
and well–developed cell line requires: 1). A strong promoter strength so that genes can express
effectively; 2) amplification of the system to give a reasonable system scale to exploit the
production potential of the cell factory.
Host cell engineering is

Antibodies : Our Body 's Weaponry Essay
Antibodies: Our Body's Weaponry
1: Introduction
Antibodies (Ab) or Immunoglobulins (Ig) are large diversities of 'Y' shaped glycoprotein molecules.
The paratope which is at the tips of the 'Y' shaped molecule are extremely specific and exceptional
to a particular epitope of an antigen (Ag) molecule. Upon binding to the antigen, antibodies can
elicit an immune reaction in response to the antigen. Antibodies which are circulating in the lymph
fluid or blood plasma are produced by B lymphocytes (Plasma B cells & Memory B cells). Hence,
they play an important role in humoral immunity under Adaptive Immune System. There are five
isotypes of antibodies namely IgA, IgD, IgE, IgG and IgM. In the following sections, the chemistry
behind the structure and the physiology of antibody response will be discussed. In addition,
applications of antibody molecules will be elaborated.
2: Structure of Antibody
Antibodies are made up of two identical heavy (H) chains and two identical light (L) chains as
shown in Figure 1 below. Both the heavy and light chains consist of variable domains and constant
domains. The variable domains (VH & VL shown in red in Figure 1) which are at the tip of 'Y'
shaped molecules are responsible for the specificity as it is unique to a particular type of antigen.
This is known as the antigen binding site (Fab). To ensure specificity, grooves present on top of Fab
region must have a complementary shape with the epitope of the antigen. Constant region of the
antibody

Monoclonal Antibodies Are An Essential Tool For Medicine
A monoclonal antibody is a monospecific antibody which is created from identical immune cells
that happen to be clones from a unique parent cell. Typically, monoclonal antibodies are the product
of the fusion between a mouse's spleen cells injected with desired antigens and myeloma cells.
These fused hybrid cells are able to work together due to the spleen cell providing hypoxanthine–
guanine–phosphoribosyl transferase (HGPRT), while the myeloma cell has traits that are similar to a
cancer cell that makes it immortal. This mixture creates clones with an ability to bind to specific
antigens. With nearly any substance, the production of monoclonal antibodies that can bind to those
substances in order to detect and purify them is a possibility. This is why monoclonal antibodies are
an essential tool for medicine.
There are certain types of treatments that are associated with monoclonal antibodies. Monoclonal
antibody therapy uses antibodies to bind to specific cells or proteins in order to stimulate one's
immune system in order to attack those specific cells. It can be used for autoimmune diseases by
inhibiting human immunoglobulin or attaching to activated T–cells and preventing kidney transplant
rejections. One major use for monoclonal antibodies is for cancer treatment, specifically lung
cancer. A simple definition for the monoclonal antibodies' role in cancer treatment is that it binds
only to cancer cell–specific antigens in order to activate an immunological response

The Expression Of Matriptase Centered On Lung Cancer Cells
The Expression of Matriptase centered networking proteins in Lung Cancer Cells
Runyu Zhong1 Chen–yong Lin2 Michael D Johnson2
1Department of Biochemistry & Molecular and Cellular Biology and
2Lombardi Cance Center, Georgetown University Medical Center, 3900 Reservoir Rd., NW,
Washington DC, 20057–1455
Abstract Pulmonary carcinoma, also known as Lung Cancer, in among the most prevalent and
thermal kinds of cancers in the world. A network around Matriptase including it 's inhibitor HAI–1,
HAI–2 and it 's downstream substrate prostasin play a significant role in both the epithelia
construction in normal epithelial cells and tumor development and progression in cancer cells. My
research focuses on the expression of matriptase, HAI–1, HAI–2 and prostasin in lung cancer cell
line NCI–H209, NCI–H292 and NCI–H1944 by means of Western blot and Inmunoflurescense.
Antibodies M23, M19 and DC16 are used to recognize matriptase, HAI–1 and HAI–2, respectively
and antibidies YL89, YL11 and YL10 are used to recognize prostasin in both experiment. All the 4
proteins in the network are detected to express in all cells line used in research and they express both
on cells menbrane and inside cells in NCI–H1944. Both HAI–1 and HAI–2 can act as inhibitors to
both matriptase and prostasin while HAI–1 is the predominant inhibitor. This network should be
very essential to the oncogenesis and metastasis of lung cancer cells.
Introduction
Pericellular proteolysis plays important roles in many

Bevacizumab : An Anti Vegf Recombinant Humanized Igg ¬ 1...
Bevacizumab is an anti–VEGF recombinant humanized IgG¬1 monoclonal antibody (rhuMAb)
angiogenesis inhibitor that is indicated as supplemental chemotherapy for metastatic cancers
including colorectal carcinoma, breast cancer, and renal cell carcinoma, as well as advanced non–
squamous non–small cell lung cancer.1,3,4 It has also been approved as a second–line single agent
therapy for glioblastoma multiform.3,4 Characteristic to all IgG monoclonal antibodies is the
presence of two fragment–antigen binding (Fab) domains that are covalently bound to a constant
(Fc) region.2 Bevacizumab is available for intravenous administration after dilution with 0.9%
Sodium Chloride Injection USP with recommended dosing regimens ranging from 5 mg/kg to 15
mg/kg every 2–3 weeks, depending on the type of malignancy.3,4
Mechanism of Action
Overexpression of vascular endothelial growth factor (VEGF) promotes development of tumor–
supportive vasculature, cell survival and migration, and vascular permeability. The expression of
VEGF is regulated via several mechanisms including oxygen tension, autocrine and paracrine
signaling, and oncogenic signaling.5 VEGF is a homodimeric glycoprotein that binds to VEGF
receptors 1 and 2 (VEGFR–1 & VEGFR–2) with high affinity (K¬d ~ 1–10 pM and Kd ~ 10–100
pM, respectively) on the extracellular surface of endothelial cells.5,7 Activation of VGFR, a tyrosine
kinase receptor, prompts receptor dimerization and autophosphorylation that initiates signal
transduction

Difference Between A Pharmaceutical And A Biologic
UNIVERSITY OF QUEENSLAND
SCHOOL OF CHEMISTRY AND MOLECULAR BIOSCIENCES
BIOT7018 BIOLOGICS
Assignment 1 – (Weeks 1, 2, 3 & 4)
SECTION A Subjective Questions associated with Lecture Material
1. What is the difference between a pharmaceutical and a biologic? 2.5 marks
Pharmaceuticals are small molecules manufactured in machines, while biologics are big molecules
made in living cells.
Pharmaceutical copies are called generics while for biologics the term is a biosimilar. Why is the
naming different for biologics? 2.5 marks
The biosimilar can not be called generic because are not clinically interchangeable. The biosimilar
do not have the same chemical active ingredient of the novel product as the generic drug. In
comparison with a generic, the biosimilar to be approved needs to be have clinical and preclinical
studies while the generic do not require this studies but pharmacokinetics tests.
2. What are the broad strategies for therapy using biologic medicines? 5 marks
Some of the strategies used in biologic medicines are:
Inhibit the over expression of mediators of disease.
Supplement growth factor, hormone or cytokine deficiencies, which can enhance immune response
through receptors and the signal transduction cascades subsequently.
Enzyme replacement therapy for the treatment of lysosomal storage diseases
Target tumour binding for drug delivery and tumor cell death.
Decreasing the activity of the immune system using immune–modulators to reduce inflammation.
3.

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