Monoclonal Antibodies & Immunotherapy in Cancer

Introduction

• A monoclonal antibody (mAb) is an immunoglobulin from a single B-cell clone recognising one epitope on a tumour antigen or growth-factor receptor; mAbs are large, parenterally-given molecules with a long plasma t½ of days–weeks, distinct from oral small-molecule kinase inhibitors.
• Four broad cancer-cell eradication mechanisms of a mAb: (1) block ligand/receptor function (cetuximab, trastuzumab); (2) recruit immune cells & complement to the antigen–antibody complex (ADCC, CDC, ADCP); (3) modulate immune-cell function (checkpoint inhibitors); (4) carry toxins/radionuclides as cytotoxic payloads (ADCs, radioimmunoconjugates).
• Milestones: Köhler & Milstein (1975, hybridoma; 1984 Nobel); rituximab (1997, first oncology therapeutic antibody); ipilimumab (2011, first checkpoint inhibitor); tisagenlecleucel (2017, first CD19 CAR-T); Allison & Honjo 2018 Nobel for checkpoint inhibition.
• Over 40 antibody-based therapeutics are FDA-approved for cancer; routinely combined with cytotoxic chemo, pathway-targeted drugs or radiotherapy (cell death promotes cytotoxic-T-cell infiltration, rationalising combination immunotherapy).