Role of antibody engineering in generation of derivatives starting from MOv19 MAb: 40 years of biological/therapeutic tools against folate receptor alfa.

Abstract

In the 1980s, we developed and characterized numerous murine monoclonal antibodies (MAbs) directed against human tumor-associated antigens. This mini review is focused on the generation of derivatives of an anti-folate receptor α (FRα) MAbs, named MOv19, exploiting the antibody-engineering progresses in the last 40 years. The FRα location on the luminal surface of proliferating epithelial cells, inaccessible to circulation, versus its over-expression in the entire surface of numerous carcinomas suggested a role for anti-FRα MAbs in the diagnosis and/or treatment of solid tumors. Presently, two MOv19 derivatives are in clinical trials: a chimeric resurfaced version in an antibody-drug conjugate format (SORAYA trial, 2022) and the murine scFv in a second generation chimeric antigen receptor, CAR-T (Phase Ia, 2021). MOv19 and its derivatives could be considered a relevant example that well-characterized anti-tumor murine Mabs and antibody engineering could be combined to generate useful therapeutic tools.