2. WHAT ARE ANTIBODIES….
An antibody is a protein used by the immune
system to identify and neutralize foreign objects
like bacteria and viruses.
Each antibody recognizes a specific antigen
unique to its target.
Monoclonal antibodies (mAb) are antibodies
that are identical because they were produced
by one type of immune cell, all clones of a
single parent cell.
Polyclonal antibodies are antibodies that are
derived from different cell lines.
3. APPLICATION OF MABS:
The application of monoclonal antibodies can be
broadly categorized as:
a) Diagnostic application
b) Therapeutic application
c) Catalytic MAb (Abzymes)
4. (A) DIAGNOSTIC APPLICATION :
MAbs are utilized in diagnostic kits for the
diagnosis of various infectious diseases,
detecting pregnancy, monitoring drug levels,
matching histocompatibility antigen, cancer and
in immune scintigraphy.
FDA licensed a new diagnostic imaging agent
that can determine the extent of disease in
patients diagnosed with small cell lung cancer
(SCLC). Because these agents can detect tumor
in different part of the body at one time.
Other monoclonal antibodies allows rapid
diagnosis of hepatitis, influenza, herpes,
5. DIAGNOSTIC APPLICATION
A monoclonal antibody can be used
to detect pregnancy in only 14 days
after conception.
Their selective binding property
low levels of human corionic
allow detection of
gonadotropin (HCG) in urine and
serum.These tests approach the
accuracy of serum beta HCG
radioimmuno assay for
confirmation of normal pregnancy
or evalution of possible abnormal
pregnancy.
6. THERAPEUTIC APPLICATION
Organ transplantation
For the treatment of solid organ transplant rejection,
several MAbs
against T cell antigens have been evaluated. 'The most
successful of
these is orthrochrome OKT3 which was first MAb to be
licensed for
human use.
The murine intact IgG antibody, directed against CD3
antigen on T
lymphocytes, is used unconjugated to effectively reverse
acute
rejection episodes with renal, hepatic, cardiac and combined
7. MONOCLONAL ANTIBODIES FOR CANCER
TREATMENT
There are three mechanisms that could be responsible for
the cancer treatment:
1. mAbs act directely when binding to a cancer specific
antigens and
induce immunological response to cancer cells. Such as
inducing
cancer cell apoptosis, inhibiting growth, or interfering with a
key
function.
2. mAbs may be modified for delivery of a toxin, radioisotope
[RADIOIMMUNOTHERAPY], cytokine or other active
conjugates.
3. It is also possible to design bispecific antibodies that can
bind with their Fab regions both to target antigen and to a
8. WHEN A MONOCLONAL ANTIBODY
ATTACHES TO A
CANCER CELL, IT CAN : Make the cancer cell
more visible to the immune system.
ex. Rituximab
• Block growth signals
ex. Cetuximab used for colon
cancer and block epidermal
growth factors.
9. Stop new blood vessels formation (angiogenesis)
Ex.Devacizumab (Avastin) acts on vascular
endothelial growth factor (VEGF).
Deliver radiation to cancer cells by binding to
radioactive element ex. Zevalin used for non-
hodgkin lymphoma.
powerful drugs into cancer cells and kills the
cancer cell. Ex. Kadcyla in breast cancer.
10. FDA-APPROVED MONOCLONAL ANTIBODIES
FOR
CANCER TREATMENT :
1. Ibritumomab (Zevalin)
2. Panitumumab (Vectibix)
3. Rituximab (Rituxan)
4. Tositumomab (Bexxar)
5. Trastuzumab (Herceptin)
6. Non-Hodgkin's lymphoma
7. Colon cancer
8. Non-Hodgkin's lymphoma
9. Non-Hodgkin's lymphoma
10. Breast cancer
11. CONJUGATED MONOCLONAL ANTIBODY
THERAPY:
Toxins or radioactive isotopes
are bound to the constant
region of the mAbs.
When the mAb binds to
the surface cells of a tumor
the toxin or radioactivity
will kill the cancer cells and
all cells within a certain radius
(a killing zone).
In this way cancer cells
within the tumors will be
12. RADIOIMMUNOTHERAPY:
Involves the use of
radioactively conjugated
Murine antibodies against
cellular antigens
Eg.; Tositumomab -----
non-Hodgkins lymphoma
13. AUTOIMMUNE DISEASES:
Monoclonal antibodies used for autoimmune diseases
include infliximab and adalimumab, which are
effective in
rheumatoid arthritis, Crohn's disease and ulcerative
Colitis by their ability to bind to and inhibit it.
Omalizumab inhibits human immunoglobulin E (IgE)
and is
useful in moderate-to-severe allergic asthma.
14. 3.CATALYTIC MONOCLONAL ANTIBODY
(ABZYMES)
The binding of an antibody to its antigen and
binding of enzyme to its substrate both involves
weak, non covalent interactions and exhibits high
specificity and often high affinity.
But an antigen is not altered by antibody, where
as an enzyme alters the substrate and as a result
the binding by catalyzing a chemical change.
The enzyme uses its binding energy to stabilize
the transition state of substrate. thus reducing
activation energy for chemical modification of
bound substrate.
Similarities between antigen-antibody interaction
and enzyme substrate interaction have led Lerner
and his colleagues to explore the probability of
enzyme like action of some antibodies.
15. MONOCLONAL ANTIBODIES IN DRUG
TARGETING:
The concept of using specific antibodies
conjugated with
toxic or isotopically labelled materials for specific
sites
and drug localization is not new.
This concept with the development of MAbs and
hybridoma technology have gained wide
appreciation in their use. The use of monoclonal
antibodies to target drugs to specific cell types is
a promising approach.
