Journal
BRITISH JOURNAL OF CANCER
Volume 124, Issue 6, Pages 1037-1048Publisher
SPRINGERNATURE
DOI: 10.1038/s41416-020-01225-5
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Funding
- Janssen Pharmaceutical Companies of Johnson Johnson
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Bispecific antibodies redirecting CD3+ T cells to target tumors hold promise as an immunotherapeutic strategy. Despite early success, challenges such as recruiting counterproductive T cell subsets, systemic cytokine release, immune checkpoint molecule expansion, and an immunosuppressive tumor microenvironment need to be overcome for optimal clinical benefit.
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 x anti-CD19 bispecific antibody blinatumomab (Blincyto(R)) for the treatment of relapsed/refractory B-cell acute lymphoblastic leukaemia, similar to 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.
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