Bispecific antibodies: advancing precision oncology

Abstract

T cell engagers; Bispecific antibodies; Immunotherapy

Activadores de células T; Anticuerpos biespecíficos; Inmunoterapia

Activadors de cèl·lules T; Anticossos biespecífics; Immunoteràpia

Bispecific antibodies (bsAbs) are engineered molecules designed to target two different epitopes or antigens. The mechanism of action is determined by the bsAb molecular targets and structure (or format), which can be manipulated to create variable and novel functionalities, including linking immune cells with tumor cells, or dual signaling pathway blockade. Several bsAbs have already changed the treatment landscape of hematological malignancies and select solid cancers. However, the mechanisms of resistance to these agents are understudied and the management of toxicities remains challenging. Herein, we review the principles in bsAb engineering, current understanding of mechanisms of action and resistance, data for clinical application, and provide a perspective on ongoing challenges and future developments in this field.

We thank Alan Russell and Michael Dickinson for their helpful suggestions and review of the manuscript. M.H is supported by a Sociedad Española de Oncología Médica (SEOM) fellowship and CRIS Cancer Out-Back program; G.P is supported by the CaixaResearch Advanced Oncology Research Program supported by ‘la Caixa’ Foundation (LCF/PR/CE07/50610001); E.G is supported by the CaixaResearch Advanced Oncology Research Program supported by ‘la Caixa’ Foundation (LCF/PR/CE07/50610001); L.L.S holds the BMO Chair in Precision Cancer Genomics; T.M.S. is funded through a collaboration with Roche; L.A. is supported by the Peter Mac Foundation Discovery Partner Fellowship.