T cell-redirecting bispecific antibodies in cancer immunotherapy: recent advances.

Abstract

Globally, cancer is a critical illness which seriously threatens human health. T-cell-based cancer immunotherapy for some patients has demonstrated impressive achievements including chimeric antigen receptor T cells, immune checkpoint inhibitors and T cell-redirecting bispecific antibodies (TRBAs). TRBAs recruit T cells to lyse cancer cells bypassing the antigen presentation through the major histocompatibility complex pathways. In this review we summarized the TRBAs formats, biophysical characteristics, the preclinical and clinical trial results, as well as the challenges faced by TRBAs in tumour therapy. Herein the relevant literature and clinical trials from the PubMed and ClinicalTrials.gov database. The advances in protein engineering technology have generated diverse TRBAs format which can be classified into two categories: IgG-like TRBAs and non-IgG-like TRBAs. Multiple applications of TRBAs showed encouraging curative effect and entered clinical trials for lymphoid malignancy and solid tumour. TRBA is a powerful tool for the cancer treatment and the clinical studies showed potent anti-tumour efficacy in hematologic malignancies. Although the clinical outcomes of TRBAs in solid tumours are less satisfied than hematologic malignancies, many preclinical antibodies and combination therapies are being evaluated.