Development and Characterization of a Neutralizing Anti-idiotype Antibody Against Mirvetuximab for Analysis of Clinical Samples

Abstract

Antibody-drug-conjugates (ADCs) are an emerging class of biological therapeutics. Mirvetuximab soravtansine is a novel folate receptor alpha (FRα)-targeting ADC which represents a potential new treatment for patients with ovarian and other FRα-positive cancers. Since patient immune responses to biological therapeutics may negatively affect drug efficacy and patient safety, regulatory authorities require rigorous monitoring of patient samples. Taking advantage of the immune system's ability to generate highly specific antibodies, the field has turned to anti-idiotype antibodies as powerful tools for the development of sensitive and specific bioassays. Here, we report the generation and characterization of a highly specific neutralizing anti-idiotype antibody directed against M9346A, the antibody moiety of mirvetuximab soravtansine. The anti-idiotype antibody recognizes M9346A with double-digit picomolar affinity, competes with folate receptor antigen for binding to M9346A, and can be used to develop both anti-drug-antibody and neutralizing antibody assays.

Therapeutic strategies targeting folate receptor α for ovarian cancer

“…Since then, two derivatives of MOv19 have entered the clinical trials. One is M9346A ( 78 ), and the other is chimeric antigen receptor (CAR) composed of a MOv19 anti-FRα specific single chain variable fragment ( 79 ). M9346A is the anti-FRα antibody component of MIRV ( 80 ).…”

“…A novel Tandem-CAR encoding an anti-FRα scFv, an anti-MSLN scFv, and two peptide sequences of IL-12 were designed to improve the efficacy, infiltration, persistence, and proliferation of CAR-T cell in ovarian cancer ( 107 ). Furthermore, CAR T cells, composed of MOv19 anti-FRα-specific single chain variable fragment fused to 4-1BB and TCRzeta signaling domains (MOv19-BBZ), is currently evaluated by a phase I clinical trial in recurrent high grade serous ovarian cancer patients ( 78 ).…”