María Natalia Gandur Quiroga, Chief of the Division of Genitourinary Medical Oncology at the Ángel H. Roffo Oncology Institute, posted on X about recent paper by Romane Martineau et al., titled “Fc Effector Function of Immune Checkpoint Blocking Antibodies in Oncology” published on Wiley.
Authors: Romane Martineau, Sandrine Susini, Aurelien Marabelle
“Checkpoint inhibitors and Fc functions: key findings in oncology immunotherapy.
Immune checkpoints (CTLA-4, PD-1, PD-L1, LAG3) have revolutionized oncology, enabling durable remissions in advanced cancer.
Mechanisms of action:
- CTLA-4 (Ipilimumab): Tumor-specific Treg depletion mediated by FcγR.
- PD-1/PD-L1: Pure receptor blockade, though some antibodies (e.g., Avelumab) retain Fc functions (ADCC).
- LAG3 (Relatlimab): Combination with Nivolumab improves PFS in metastatic melanoma.
Efficacy vs. Toxicity:
- Direct dose-toxicity relationship for anti-CTLA-4.
- Fixed, spaced doses (e.g., 480 mg Q4W for Nivolumab) improve quality of life.
Hyperprogression: Seen in up to 20% of patients, linked to FcγRIIb in immunosuppressive macrophages.
Innovation: Fc-enhanced antibodies (e.g., botensilimab) show greater efficacy and Treg depletion in solid tumors.
Takeaway: Fc affinity and genetic polymorphisms shape clinical outcomes. New frontiers in immunological precision!”
María Natalia Gandur Quiroga is a Medical Oncologist and Chief of the Division of Genitourinary Medical Oncology at the Ángel H. Roffo Oncology Institute in Buenos Aires, Argentina. She is a Professor of Medicine at the University of Buenos Aires at the Oncologists Post Graduates Studies. Her research focuses on clinical trials with aims to improve the treatment of patients with urologic tumors. She is an active member of the European Association for Cancer Research, Argentinian Medical Association and American Society of Clinical Oncology.