Monoclonal Antibodies in Oncology
Therapeutic monoclonal antibodies target tumor-associated antigens to block growth signals, recruit immune effectors, and deliver cytotoxic payloads.
## Overview
Monoclonal antibodies (mAbs) are engineered immunoglobulins that bind specific tumor-associated antigens with high affinity and selectivity. Therapeutic mechanisms include blocking receptor signaling, inducing antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and direct apoptosis induction.
## Anti-HER2 Antibodies
**Trastuzumab (Herceptin)** binds HER2 domain IV, blocking receptor dimerization and signaling, inducing ADCC, and downregulating HER2. Used in HER2-amplified breast and gastric cancers. Cardiotoxicity (non-cumulative, reversible LVEF decline) requires monitoring; avoid concurrent anthracyclines.
**Pertuzumab** binds HER2 domain II (dimerization domain), preventing HER2-HER3 heterodimerization. Combined with trastuzumab (dual HER2 blockade) in metastatic and neoadjuvant breast cancer.
**Trastuzumab emtansine (T-DM1)** is an antibody-drug conjugate delivering DM1 (microtubule inhibitor) directly to HER2+ cells.
## Anti-CD20 Antibodies (B-Cell Malignancies)
**Rituximab** binds CD20 on B cells, mediating ADCC, CDC, and direct apoptosis. Used in B-cell NHL and CLL. Obinutuzumab (glycoengineered type II anti-CD20) has enhanced ADCC and superior activity in CLL vs. chlorambucil.
## Anti-VEGF: Bevacizumab
Bevacizumab binds circulating VEGF-A, preventing angiogenesis. Used in colorectal, lung, ovarian, glioblastoma, and cervical cancers. Toxicities: hypertension, proteinuria, thromboembolism, impaired wound healing, bowel perforation.
## Anti-EGFR Antibodies
Cetuximab and panitumumab bind EGFR extracellular domain. RAS mutation testing is mandatory before use in colorectal cancer — KRAS/NRAS mutations predict lack of benefit. Infusion reactions are common with cetuximab (premedicate).
## Key Takeaways
- mAbs act via receptor blockade, ADCC, CDC, and direct pro-apoptotic signaling
- Trastuzumab requires HER2 overexpression/amplification confirmation; monitor cardiac function
- Bevacizumab inhibits angiogenesis by neutralizing VEGF-A
- KRAS/NRAS testing is mandatory before cetuximab or panitumumab in colorectal cancer