2. Protein produced by B-lymphocyte
Highley specific for binding
Bind to the known structure of antigen
3. Pro-moiety /pro-agent/bio reversible derivative
1st used by Albert in1958
Designed to overcome barrier by chemical approach instead
of formulation approach
E.g. Human enzyme cacarboxypeptidaseA1+Methotrexate
(phenylalanine/tyrosine based)
4. Types of cancer therapies
Radiotherapy-High energy radio beams are used to kill
cancer cells
Surgery-removal of tumour by surgery
Chemotherapy-Drugs are used in combinations to block
multiple cellular functions
Targeted therapy-drugs are used against predetermined
cellular targets
5. Acts as a cytotoxic agent generating system at tumour
site
Reduce toxicity and increase selective toxicity at
tumour cells
Principle
This therapy has three steps
1. Administration of antibody enzyme conjugate
2. Administration of clearing agent
3. Administration of prodrug molecule
6. Need
Improve cellular specificity
Resistance to the normal cell growth
Evolution of targeting
In the 1980s decade(antibody drug conjugate prepared)
MTDP-Molecular Targets Developing Programme run
by National Cancer Institute, USA.
7. Stable, covalent linkage between enzyme and antibody
Defined composition, molecular weight
Antigen combining site ,enzyme active site must be free
Act as Heterobifunctional coupling agent
tumor associated antigen
E.g.
Ovarian cancer-CA 125
Breast cancer- CA15-3
8. What is the need??
After specific time clearing agent will be administered
Clearing agent clears the all AEC molecules
In middle trials has been took place to remove this step
to make therapy easy
9. Only after successful AEC clearance
As it’s prodrug is inactive
“Prodrug reach at door of every cell”
Drug released by enzyme only at tumour cell
10. AEC will bind to the cancer cell
Clearance of AEC from blood
Highly cytotoxic pro-drug will reach all over
the body
Drug released only at tumour site
11. Chemotherapy
Kills all rapidly growing and
dividing cells
Same cells at intestinal
epithelium, line of digestive track,
bone marrow
Effect is dose dependant
ADEPT
Specify difference between normal cells and
cancerous cells
Fundamental difference is tumour cells
mutations are presents causing uncontrolled
proliferation
Defective proteins produced by these genes
are the prime targets
Comparison with chemotherapy
12. Challenges
Selection of enzyme with no human homologue also
with immune compatibility
Skilled professionals
Achievements
New door has been opened for treatment cellular level
Use of immunosuppression in short term use