Introduction to target specific action in cancer treatment a recent focus on monoclonal antibody therapy

1. Name-Jayita Das
Dr BC Roy College Of Pharmacy And AHS
Dr Meghnad Saha Sarani Bidhan Nagar
Durgapur-713206
West Bengal, India.

2.  Introduction To Cancer.
 Cancer Statistic.
 Introduction to Monoclonal Antibody.
 Why Monoclonal Antibody directed cytotoxic
therapy.
 Antibody Drug Conjugate.
 How They Work.
 Conclusion.
 Reference .

3. what is cancer ?
 Cancer is a disease involving abnormal cell growth
with the potential to invade or spread to others
part of the body, promoting blood vessels
contraction and invasion of tissue formation of
metastases . Not all tumours are cancerous;
benign tumours do not spread to the others parts
of body and other is malignant tumour.
 Possible signs and symptoms include lumps,
abnormal bleeding, prolonged cough, excessive
weight loss etc.
 Tobacco use is the cause of about 22% of cancer
death & 10% is due to obesity, consumption of
alcohol and others genetic defect.

4. Metastasis is the spread of
cancer from one organ or
parts of the body to another
without being directly
connected .

5.  Each year the American Cancer Society estimates
the number of new cancer cases and deaths that
will occur in the current year. Mortality data
were collected by the National centre for Health
statistics.
 In 2016, 16,85210 new cancer cases and 5,95,690
cancer deaths are projected to occur in United
States .
 In India one women dies of cervical cancer every
8 min. For every 2 women newly diagnosed with
breast cancer, one women dies in it. Every year
new cancer patients registered over 7lakh and
cancer related deaths 5,56,400.

6.  Current cancer therapies provide only a 40%
probability that a patients diagnosed with
cancer today will be alive in 5 years’ time.
Furthermore the relatively low therapeutic
index of many anti-cancer drugs causes
severe toxic effect on normal tissues.
 As a consequence new cancer therapies are
being investigated which aim to specifically
target tumour cells and sparing normal
individuals from exposure to the cytotoxic
agent . One such approach is Monoclonal
Antibody directed cytotoxic therapy.

7.  Monoclonal antibodies (mAb) are antibodies that
are made by identical immune cells and are all
clones of unique parent cell. Monoclonal
antibodies can have monovalent affinity, in that
they bind to the same epitope.
 Monoclonal antibody therapy is a form of
immunotherapy that uses monoclonal antibodies
to bind monospecifically to certain cells. This may
then stimulate the patients immune system to
attack those cells.
 Monoclonal antibodies directed cytotoxic agents
are potent, specific and relatively non toxic .

8.  Antibody-drug conjugates or ADCs are an important class
of highly potent biopharmaceutical drugs designed as a
targeted therapy for the treatment of people with cancer.
 It Contain a monoclonal antibody, a stable linker based on
chemical motifs like disulphide , hydrazones or peptides (
cleavable), and thioethers ( non-cleavable),control the
distribution and delivery of potent cytotoxic agent. The
availability of better and more stable linkers has changed
the function of the chemical bond. The type of linker,
cleavable or no cleavable, lends specific properties to the
cytotoxic (anti-cancer) drug. For example, a non-cleavable
linker keeps the drug within the cell. As a result, the entire
antibody, linker and cytotoxic (anti-cancer) agent enter the
targeted cancer cell where the antibody is degraded to the
level of an amino acid. The resulting complex – amino acid,
linker and cytotoxic agent – now becomes the active drug.
In contrast, cleavable linkers are catalyzed by enzymes in
the cancer cell where it release the active agent.

10.  Monoclonal antibodies are designed to
function in different ways.
 Antibody drug conjugates- It is a unique
combination of a targeted monoclonal
antibody a stable linker and a potent
cytotoxic, they design to deliver anti-cancer
agents directly to the tumour cell in a
targeted manner to limit systemic
exposures. Based on preclinical studies the
monoclonal antibody component of ADC lines
to the target antigen on the tumour cells
.Surface target antigens are preferentially or
exclusively expressed on the surface of
cancer cells to provide a tumour specific
binding site for the monoclonal antibody.

11. Monoclonal antibodies has the ability to
persist in circulation over time allowing
prolonged exposures to cancer cells and
become internalized by the cancer cell ,
stable linkers conjugate potent cytotoxic
agents and are designed to allow ADC to
remain inactive while in circulation, linker
stability and circulation controls the
distribution and delivery of cytotoxic agents
to the target cells . Monoclonal antibody
component of ADC may possess its own anti-
cancer activities include( prevention of
signalling, antibody dependent cellular
cytotoxicity and induction of apoptosis ).
Upon binding to the target antigen the
ADC internalized through a process
known as receptor mediated endocytosis
Followed by lysosomal degradation of the
ADC antigen complex and release the
potent cytotoxic agent , which interacts
with critical cellular machinery to elicit
cell death . In this way it causes death of
cancer cell.

12. ∆ To date, only 3 ADCs have received market
approach however, after a request from the U.S
Food & drug Administration (FDA) Pfizer/Wyeth ,
the developer and marketer of the 1st ADC to
receive marketing approval in 2001 for
treatment of patient with acute myelogenous
leukaemia and in breast cancer.
∆ There are several other ADCs under Preclinical
trial .
∆ The current objectives are aimed at improving
the efficacy and therapeutic index of
immunoconjugates by optimizing selectivity and
potency.

13.  Pamela A Trail, Albert b Bianchi. Monoclonal
antibody conjugates in treatment of
cancer.1999;11:584-588.