The extraordinary sensitivity and specificity of T cells for their cognate antigen make them a highly attractive cancer therapeutic. However, the rarity of tumor-reactive T cells in cancer patients, the difficulty isolating them in sufficient numbers for adoptive immunotherapy, and the unpredictable persistence of transferred cells have been significant obstacles to broad application. Technologies that enable genetic modification of T cells have been refined and are being used to redirect the specificity of T cells to tumor antigens. An issue the field is now grappling with is how the diverse phenotypic and functional heterogeneity in T cells that could potentially be genetically modified can be capitalized upon to enhance the efficacy, safety, and reproducibility of cancer immunotherapy.
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