Adoptive immunotherapy for cancer: harnessing the T cell response

Adoptive immunotherapy for cancer: harnessing the T cell response

2018 | Nicholas P. Restifo, Mark E. Dudley, and Steven A. Rosenberg
Adoptive immunotherapy for cancer involves transferring T cells, either naturally occurring or genetically engineered, to patients to target and eliminate tumour cells. This review discusses recent advances in using adoptively transferred T cells to mediate tumour cell eradication, focusing on antigen targeting, gene engineering, and identifying effective T cell subsets. T cells recognize tumour antigens through MHC molecules and can be activated by tumour-associated antigens. Tumour-infiltrating lymphocytes (TILs) can be isolated and expanded from tumours, and their transfer can lead to tumour regression. However, TILs may be suppressed by immunosuppressive factors in the tumour environment. Removing these factors can enhance TIL activation and tumour eradication. TILs can be expanded in culture and reinfused into patients, leading to durable remission. Tumour-specific T cells can recognize antigens from mutated genes, viral products, or epigenetic changes. These antigens are attractive targets because they are not expressed by normal tissues. T cells can also target tumour vasculature and stroma, which are essential for tumour growth. T cell-based therapies, such as adoptive cell transfer (ACT), have shown promise in treating metastatic melanoma and other cancers. However, challenges remain, including the need for effective antigen targeting and minimizing toxicity. Gene engineering allows for the creation of T cells with high specificity for tumour antigens, improving therapeutic outcomes. T cell differentiation states, such as naive, central memory, and effector memory T cells, play a crucial role in immunotherapy. CD8⁺ T cells are particularly effective in tumour rejection, while CD4⁺ T cells can enhance CD8⁺ T cell function and directly contribute to tumour elimination. The use of chimeric antigen receptors (CARs) and genetically engineered T cells has expanded the range of tumour types that can be targeted. Despite these advances, challenges remain in achieving durable remission and minimizing toxicity. Strategies to deplete the immunosuppressive tumour microenvironment and modulate T cell differentiation are being explored to improve therapeutic outcomes. Overall, adoptive immunotherapy represents a promising approach in cancer treatment, with ongoing research aimed at enhancing its efficacy and safety.Adoptive immunotherapy for cancer involves transferring T cells, either naturally occurring or genetically engineered, to patients to target and eliminate tumour cells. This review discusses recent advances in using adoptively transferred T cells to mediate tumour cell eradication, focusing on antigen targeting, gene engineering, and identifying effective T cell subsets. T cells recognize tumour antigens through MHC molecules and can be activated by tumour-associated antigens. Tumour-infiltrating lymphocytes (TILs) can be isolated and expanded from tumours, and their transfer can lead to tumour regression. However, TILs may be suppressed by immunosuppressive factors in the tumour environment. Removing these factors can enhance TIL activation and tumour eradication. TILs can be expanded in culture and reinfused into patients, leading to durable remission. Tumour-specific T cells can recognize antigens from mutated genes, viral products, or epigenetic changes. These antigens are attractive targets because they are not expressed by normal tissues. T cells can also target tumour vasculature and stroma, which are essential for tumour growth. T cell-based therapies, such as adoptive cell transfer (ACT), have shown promise in treating metastatic melanoma and other cancers. However, challenges remain, including the need for effective antigen targeting and minimizing toxicity. Gene engineering allows for the creation of T cells with high specificity for tumour antigens, improving therapeutic outcomes. T cell differentiation states, such as naive, central memory, and effector memory T cells, play a crucial role in immunotherapy. CD8⁺ T cells are particularly effective in tumour rejection, while CD4⁺ T cells can enhance CD8⁺ T cell function and directly contribute to tumour elimination. The use of chimeric antigen receptors (CARs) and genetically engineered T cells has expanded the range of tumour types that can be targeted. Despite these advances, challenges remain in achieving durable remission and minimizing toxicity. Strategies to deplete the immunosuppressive tumour microenvironment and modulate T cell differentiation are being explored to improve therapeutic outcomes. Overall, adoptive immunotherapy represents a promising approach in cancer treatment, with ongoing research aimed at enhancing its efficacy and safety.
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