Estelle Baulu; Célia Gardet; Nicolas Chuvin; Stéphane Depil · 2023 · Science Advances
Paper
T cell engineering has changed the landscape of cancer immunotherapy. Chimeric antigen receptor T cells have demonstrated a remarkable efficacy in the treatment of B cell malignancies in hematology. However, their clinical impact on solid tumors has been modest so far. T cells expressing an engineered T cell receptor (TCR-T cells) represent a promising therapeutic alternative. The target repertoire is not limited to membrane proteins, and intrinsic features of TCRs such as high antigen sensitivity and near-to-physiological signaling may improve tumor cell detection and killing while improving T cell persistence. In this review, we present the clinical results obtained with TCR-T cells targeting different tumor antigen families. We detail the different methods that have been developed to identify and optimize a TCR candidate. We also discuss the challenges of TCR-T cell therapies, including toxicity assessment and resistance mechanisms. Last, we share some perspectives and highlight future directions in the field.
Analysis
This review explores the potential of T cell receptor (TCR)-engineered T cell (TCR-T) therapy as a promising alternative to CAR-T cells for treating solid tumors, detailing current progress, challenges, and future directions.
Discovery
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