Mae Woods

BACKGROUND: The wider application of T cells targeting viral tumor-antigens via their native receptors is hampered by the failure to expand potent tumor-specific T cells from patients. Here, we examine reasons for and solutions to this failure, taking as our model the preparation of Epstein-Barr virus (EBV)-specific T cells (EBVSTs) for the treatment of EBV-positive lymphoma.

Keywords CD5 Antigens, Humans, Receptors, Chimeric Antigen, Cytotoxicity, Immunologic, T-Lymphocytes, Immunotherapy, Adoptive, Animals, Receptors, Antigen, T-Cell/, chimeric antigen receptor, T cell fratricide, CD5, T cell malignancies, off-tumor toxicity, clinical trials, CAR, fratricide Abstract Chimeric antigen receptor T cells (CART) targeting lymphocyte antigens can induce T cell fratricide and require additional engineering to mitigate self-damage.

Highlights • CD5 is highly expressed in T cell malignancies and normal T cells • CD5.CAR causes full degradation of CD5 in T cells leading to fratricide resistance • CD5.CAR transiently downmodulates CD5 on target cells in trans • CD5 modulation in trans does not protect target cells from CD5.CART cells long-term Summary Chimeric antigen receptor T cells (CART) targeting lymphocyte antigens can induce T cell fratricide and require additional engineering to mitigate self-damage.