BOC Sciences is a life sciences group with its headquarters in the NY. BOC Sciences provides the most complete set of solutions in antibody-drug conjugate (ADC) drug development services in the pharmaceutical industry. Please visit https://adc.bocsci.com/ for more information.
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Brief Introduction of Antibody Drug Conjugates
1. A brief introduction of
Antibody Drug Conjugates
Address: 45-16 Ramsey Road, Shirley, NY
11967, USA
Tel: 1-631-504-6093
Fax: 1-631-614-7828
Email: info@bocsci.com
2. Theoretical increase in the therapeutic window 02
Anticancer drugs, such as folate analogs (such as
methotrexate) or DNA disruptors (such as nitrogen
mustard), target rapidly dividing cancer cells, but at the
same time affect other healthy dividing cells in the body,
causing serious side effects and limiting the dose that
can be administered reduces the scope of treatment.
The development of ADC involves the use of antibodies
to deliver highly cytotoxic drugs directly to tumor cells
without affecting other dividing cells in the body.
Therapeutic
window
Therapeutic window
Chemotherapy ADCs
Toxic dose (MTD)
Efficacious dose (MED)
Drugdose
4. Anatomy of an ADC 04
Tumor Antigen Recognition Side
• Abundance in tumors
• Minimal normal cell expression
• Internalisation
Antibody
5. Anatomy of an ADC 05
Linker & Conjugation Technologies
• Cysteine or lysine couples, or engineered
• Cleavable
⁻ Acid-labile
⁻ Protease cleavable
⁻ Disulfide linkage
• Non-cleavable
• Potential to change the number of payloads
per antibody (i.e. DAR)
Antibody
6. Anatomy of an ADC 06
ADC Payloads (Cytotoxin)
• Microtubule inhibitors
⁻ Auristatins (MMAE)
⁻ Maytansines (DM1/DM4)
• DNA damaging agents
⁻ Calicheamich
⁻ Anthracyclines
⁻ DNA cross-linking agents
⁻ DNA mono-alkylating agents
• Others (e.g. toxic proteins, RNA inhibitors)
Antibody
7. The mechanism of action of ADCs 07
1. ADC attach themselves to
antigens on the surface of cancer
cells
2. The antibody is absorbed or
internalized together with the
linked cytotoxin
3. Transport into lysosome
4. ADC is degraded in the lysosome
5. Drug release and activation in
cancer cells
6. Cytotoxicity effect and cell death
ADC
Step 1:
Antigen binding
Step 3:
Lysosomal degradation
Step 4:
Release of payload
Step 5 :
DNA or microtubule
disruption
Step 2:
Endocytosis
8. Related challenges of during the action of ADCs 08
Step 1:
Antigen binding
Step 3:
Lysosomal degradation
Step 4:
Release of payload
Step 5 :
DNA or microtubule
disruption
Step 2:
Endocytosis
Challenge: potency of
released payload must be
sufficient kill cell even at
low concentrations.
Challenge: The ADC has
to efficiently release the
cytotoxic payload in its
active form.
Challenge: mAb must
retain high affinity. A
stable linker is required
to minimize premature
release of payload and
off-target toxicity.
Challenge: inefficient
internalization due to limited
target antigen level may prevent
the cytotoxin from reaching its
threshold concentration within
the cell.
9. ADC Services of BOC Sciences 09
Antibody
modification &
conjugation
ADC
payloads
development
ADC linker
development
ADC analysis &
characterization
ADC linker
& cytotoxin
conjugations
ADC
manufacture
1
4
6 2
35
With our integrated global resources
in all aspects, our one-stop ADC
development services will provide
you with a platform that could
exponentially speed up the process of
ADC development, form ADC
formulation to clinical evaluation.
10. Address: 45-16 Ramsey Road, Shirley, NY 11967, USA
Tel: 1-631-504-6093
Fax: 1-631-614-7828
Email: info@bocsci.com
Web: https://adc.bocsci.com/