ADCS Antibody

Definition and Role of ADC Antibodies

ADC antibodies are monoclonal antibodies designed to bind specific antigens on cancer cell surfaces. They serve as homing devices, directing cytotoxic drugs to tumors while sparing healthy tissues . By leveraging the antigen-binding specificity of mAbs, ADC antibodies ensure localized payload release, improving therapeutic efficacy and safety .

Mechanism of Action

1. Antigen Binding: The ADC antibody binds to a tumor-associated antigen (e.g., HER2 in breast cancer) .

2. Internalization: The ADC-antigen complex undergoes receptor-mediated endocytosis .

3. Payload Release: Lysosomal enzymes or acidic conditions cleave the linker, releasing the cytotoxic drug .

4. Bystander Effect: Membrane-permeable payloads (e.g., deruxtecan) kill neighboring antigen-negative cells, enhancing efficacy .

Key Targets of ADC Antibodies

ADC antibodies target antigens overexpressed in cancers:

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Bispecific Antibodies

Bispecific ADC antibodies bind two antigens or epitopes, enhancing tumor specificity and internalization. For example:

• HER2/PRL-R: Targets HER2 and prolactin receptor, improving lysosomal degradation in dual-expressing cells .

• Biparatopic ADCs: Bind non-overlapping epitopes on the same antigen (e.g., HER2), increasing clustering and internalization .

Emerging Targets

• ROR1: Expressed in aggressive lymphomas and solid tumors; preclinical ADCs show promise .

• B7-H3: Overexpressed in lung and ovarian cancers; multiple ADCs in clinical trials .

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Approved ADCs

As of 2025, 13 ADCs are FDA-approved, with over 260 candidates in clinical trials . Key approvals include:

• Trastuzumab deruxtecan: HER2-low breast cancer .

• Mirvetuximab soravtansine: Folate receptor α-positive ovarian cancer .

Resistance Mechanisms

• Antigen Loss: Reduced target expression limits ADC binding .

• Lysosomal Dysfunction: Impaired payload release .

Biomarker Challenges

Most ADCs lack predictive biomarkers, though exceptions include HER2 expression for trastuzumab deruxtecan .

Future Directions

1. Dual-Payload ADCs: Deliver two drugs (e.g., DNA disruptor + immune activator) to overcome resistance .

2. Combination Therapies: Pairing ADCs with checkpoint inhibitors (e.g., pembrolizumab) to enhance immune response .

3. Site-Specific Conjugation: Improved homogeneity and stability via engineered cysteine residues or enzymatic methods .

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Global Market and Research Trends

The ADC market is projected to grow at a CAGR of 12.3% (2025–2029), driven by:

• Pipeline Expansion: 164 ADCs in active clinical trials as of 2023 .

• Geographic Reach: North America leads in approvals, while Asia-Pacific shows rapid growth in trials .