TY - JOUR TI - Overcoming the challenges associated with CD3+ T-cell redirection in cancer AU - Singh, Ajit AU - Dees, Sundee AU - Grewal, Iqbal S. T2 - British Journal of Cancer AB - The development of bispecific antibodies that redirect the cytotoxic activity of CD3+ T cells to tumours is a promising immunotherapeutic strategy for the treatment of haematological malignancies and solid cancers. Since the landmark FDA approval at the end of 2014 of the anti-CD3 × anti-CD19 bispecific antibody blinatumomab (Blincyto®) for the treatment of relapsed/refractory B-cell acute lymphoblastic leukaemia, ~100 clinical trials investigating the safety and efficacy of CD3+ bispecific T-cell redirectors for cancer have been initiated. However, despite early success, numerous challenges pertaining to CD3+ T-cell redirection in the context of cancer exist, including the recruitment of counterproductive CD3+ T-cell subsets, the release of systemic cytokines, the expansion of immune checkpoint molecules, the presence of an immunosuppressive tumour microenvironment, tumour antigen loss/escape, on-target off-tumour toxicity and suboptimal potency. The aim of the present review is to discuss novel approaches to overcome the key challenges associated with CD3+ bispecific T-cell redirection in order to achieve an optimal balance of anti-tumour activity and safety. DA - 2021/01/19/ PY - 2021 DO - 10.1038/s41416-020-01225-5 DP - www.nature.com SP - 1 EP - 12 LA - en SN - 1532-1827 UR - https://www.nature.com/articles/s41416-020-01225-5 Y2 - 2021/01/20/00:11:46 ER -