CRC Antibody

Definition and Mechanism of CRC Antibodies

CRC antibodies are immunoglobulins designed to bind antigens overexpressed or mutated in colorectal cancer cells. Their mechanisms include:

• Targeted pathway inhibition (e.g., EGFR, VEGF/VEGFR) .

• Immune checkpoint modulation (e.g., PD-1/PD-L1, CTLA-4) .

• Antibody-dependent cellular cytotoxicity (ADCC) to engage immune cells .

FDA-Approved CRC Antibodies

The following table summarizes key FDA-approved antibodies for CRC:

Sources:

Anti-Angiogenic Antibodies

• Bevacizumab (VEGF-A inhibitor) combined with chemotherapy improves OS in first-line settings (20.3 vs. 15.6 months in AVF2107 trial) .

• Ramucirumab (VEGFR-2 inhibitor) + FOLFIRI improves OS in second-line therapy (RAISE trial) .

Immune Checkpoint Inhibitors

• Pembrolizumab achieves durable responses in dMMR/MSI-H CRC (ORR: 40–55%) .

Antibody-Drug Conjugates (ADCs)

ADCs like T-DXd (anti-HER2) and SAR408701 (anti-CEACAM5) are under investigation. Key findings:

• CEA-TCB (anti-CEA bispecific antibody) + atezolizumab shows anti-tumor activity in MSS CRC .

• ADCs with novel payloads (e.g., topoisomerase inhibitors) demonstrate reduced toxicity and enhanced bystander effects .

Bispecific Antibodies

• MCLA-158 (EGFR/LGR5 bispecific) inhibits stem-like CRC cells in preclinical models .

Resistance Mechanisms

• Acquired RAS mutations post-anti-EGFR therapy necessitate ctDNA monitoring for rechallenge eligibility .

• BRAF V600E mutations correlate with poor prognosis; bevacizumab-based regimens are preferred .

Biomarker Testing Guidelines

• Mandatory testing: RAS, BRAF, and dMMR/MSI status .

• Emerging biomarkers: HER2 amplification, CEACAM5 expression .

Future Directions

• Next-gen antibodies: Bispecific/multispecific antibodies targeting EGFR/HER3 or VEGF/ANG2 .

• Combination strategies: Anti-EGFR + BRAF/MEK inhibitors for BRAF-mutant CRC .