The risk of T-cell fractricide, a situation in which chimeric antigen receptor (CAR) T cells are toxic to each other, owing to the expression of multiple shared antigens by malignant and nonmalignant cells, precludes the use of CAR T-cell-based therapies in patients with T-cell malignancies. New research indicates that targeted disruption of the CD7 gene in anti-CD7 CAR T cells largely avoids the risk of fractricide, and enables expansion of the anti-CD7 CAR T-cell population. Such an approach generated robust antitumour cytotoxicity in malignant T-cell lines and mouse models of T-cell malignancies. In in vivo experiments, anti-CD7 CAR T cells remained toxic to the unedited (CD7+) T cells and natural killer cells of the host; however, anti-CD7 CAR T cells can themselves generate an immune response to pathogens, suggesting that such an approach could be tolerated by patients.
References
Gomes-Silva D. et al. CD7-edited T cells expressing a CD7-specific CAR for the therapy of T-cell malignancies. Blood http://dx.doi.org/10.1182/blood-2017-01-761320 (2017)
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Sidaway, P. Genomic disruption of CD7 avoids fractricide. Nat Rev Clin Oncol 14, 458 (2017). https://doi.org/10.1038/nrclinonc.2017.91
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DOI: https://doi.org/10.1038/nrclinonc.2017.91