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Understanding Antibody-Drug Conjugates

Antibody-Drug Conjugates (ADCs) are targeted cancer therapies that combine monoclonal antibodies with cytotoxic drugs to specifically attack cancer cells while minimizing damage to healthy cells. ADCs consist of three main components: an antibody, a linker, and a cytotoxic drug, and they operate by binding to cancer cells, being internalized, and releasing the drug to induce cell death. While ADCs offer advantages such as target specificity and reduced toxicity, they also face challenges like potential side effects and manufacturing complexities.

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49 views30 pages

Understanding Antibody-Drug Conjugates

Antibody-Drug Conjugates (ADCs) are targeted cancer therapies that combine monoclonal antibodies with cytotoxic drugs to specifically attack cancer cells while minimizing damage to healthy cells. ADCs consist of three main components: an antibody, a linker, and a cytotoxic drug, and they operate by binding to cancer cells, being internalized, and releasing the drug to induce cell death. While ADCs offer advantages such as target specificity and reduced toxicity, they also face challenges like potential side effects and manufacturing complexities.

Uploaded by

sopanshinde
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Introduction to Antibody-Drug

Conjugates (ADCs)
• Basics for Beginners
• Presented by: [Your Name]
What Are ADCs?
• Antibody-Drug Conjugates (ADCs) are targeted
cancer therapies that combine monoclonal
antibodies with potent cytotoxic drugs.
Why ADCs?
• Traditional chemotherapy affects healthy cells.
ADCs deliver drugs specifically to cancer cells,
reducing side effects.
Basic Structure of ADCs
• ADCs have three parts:
• 1. Antibody
• 2. Linker
• 3. Cytotoxic Drug (Payload)
Monoclonal Antibody (mAb)
• mAbs are proteins that specifically bind to
antigens on cancer cell surfaces.
Linker
• Connects the antibody to the drug. Needs to
be stable in blood and release the drug inside
the cell.
Cytotoxic Drug (Payload)
• Powerful anti-cancer agents that are too toxic
to be used freely but are effective when
targeted.
Mechanism of Action – Overview
• ADCs bind to cancer cells, are internalized,
release the drug, and cause cell death.
Step 1 – Target Binding
• The antibody in the ADC binds to a specific
antigen on the cancer cell.
Step 2 – Internalization
• The cell engulfs the ADC-antigen complex
through endocytosis.
Step 3 – Payload Release
• Inside the cell, the linker is cleaved, releasing
the cytotoxic drug.
Step 4 – Cell Death
• The released drug disrupts vital cell processes,
leading to cancer cell death.
Common Payloads
• Includes drugs like MMAE (microtubule
inhibitor) and calicheamicin (DNA-damaging
agent).
Types of Linkers
• Cleavable linkers (e.g. pH-sensitive) vs Non-
cleavable (require complete degradation).
ADC Design Challenges
• Choosing the right target, ensuring linker
stability, and drug potency.
Ideal Target Characteristics
• Target should be highly expressed on cancer
cells and low on healthy cells.
Approved ADCs – Snapshot
• Examples:
• - Adcetris
• - Kadcyla
• - Enhertu
Clinical Applications
• Used in lymphomas, breast cancer, lung
cancer, and more.
Advantages of ADCs
• Target specificity, reduced systemic toxicity,
and enhanced efficacy.
Limitations of ADCs
• May still cause side effects, resistance, and are
complex to manufacture.
ADC Development Process
• Involves discovery, preclinical testing, clinical
trials, and approval.
Case Study – Kadcyla
• Used in HER2-positive breast cancer.
Combines trastuzumab with DM1.
Case Study – Adcetris
• Used in CD30-positive lymphomas. Combines
brentuximab with MMAE.
Emerging ADC Technologies
• Includes site-specific conjugation, novel
linkers, and bispecific ADCs.
Future Directions
• Combination therapies, AI-guided design, and
personalized treatment.
Safety and Side Effects
• Includes fatigue, nausea, liver toxicity, etc.
Requires careful monitoring.
Regulatory Landscape
• Regulated by FDA/EMA with strict guidelines
on safety and efficacy.
Summary of Key Concepts
• ADCs = Antibody + Linker + Drug
• Work by targeting and killing cancer cells.
FAQs / Common Misconceptions
• Q: Are ADCs chemotherapy?
• A: Yes, but targeted.
• Q: Are they safe?
• A: Safer than traditional chemo.
Thank You / Questions?
• Feel free to ask questions!
• Contact: [Your Email or Institution]

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