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Presented by-Swapnil Kale
Pharmaceutics
(M.Pharm sem-1st)
Department of Pharmaceutical Sciences R.T.M.N.U.,Nagpur-440033.
 Protein produced by B-lymphocyte
 Highley specific for binding
 Bind to the known structure of antigen
 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)
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
 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
 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.
 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
 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
 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
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
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
 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
 10.1016/j.addr.2017.09.009,by Surinder
K.Sharma
 Prodrug : challenges and Rewards , Part 1,By
Velentino J.Stella , Jefferson W.Tilley
 www.Wikipedia .com/antibody directed
enzyme prodrug therapy
Antibody directed enzyme prodrug therapy

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Antibody directed enzyme prodrug therapy

  • 1. Presented by-Swapnil Kale Pharmaceutics (M.Pharm sem-1st) Department of Pharmaceutical Sciences R.T.M.N.U.,Nagpur-440033.
  • 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
  • 13.  10.1016/j.addr.2017.09.009,by Surinder K.Sharma  Prodrug : challenges and Rewards , Part 1,By Velentino J.Stella , Jefferson W.Tilley  www.Wikipedia .com/antibody directed enzyme prodrug therapy