Unique challenges have prevented the type of fruitful development of chimeric antigen receptor (CAR) T-cell therapies for T-cell non-Hodgkin lymphomas (T-NHL) paralleling those used in B-cell malignancies. Fratricide and the risk for T-cell aplasia dominate the issues researchers face since targetable antigens are commonly shared between both normal and malignant cells (Fleischer et al., 2019; Scherer et al., 2019). Although B-cell aplasia is a risk for the CARs licensed for use in the B-cell lymphoma space, the degree of immunosuppression resulting from dampening normal T-cell function would have more devastating consequences. Focusing on antigens with restricted expression, such as CD30, could eliminate these obstacles. Unfortunately, this approach comes at the cost of limiting the number of patients who may benefit given the heterogeneity of this group of diseases. Conversely, targeting pan-T-cell antigens broadens applicability across T-NHL subtypes, but in doing so requires addressing the concerns of fratricide and T-cell aplasia.
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