Journal
HUMAN MOLECULAR GENETICS
Volume 20, Issue -, Pages R93-R99Publisher
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddr102
Keywords
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Funding
- NCI [CA094237, P50CA126752]
- NHLBI [U54HL081007]
- Leukemia and Lymphoma Society Specialized Center of Research
- [T32HL092332]
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Adoptive immunotherapy is an appealing approach to cancer treatment, with the potential for more precise targeting and reduced toxicity. While early clinical trial data using adoptive T cells against post-transplant virus-associated hematologic malignancies, lymphoma and melanoma have been promising, treating other solid tumors has proven to be more challenging. Adoptive lymphocytes have been genetically modified in many ways to improve activity and circumvent tumor evasion, including transfer of transgenic T-cell receptors and chimeric antigen receptors to redirect T cell and natural killer cell antigen specificity. Gene transfer may also allow expression of homeostatic cytokines or their receptors to overcome the lack of stimulatory signals or expression of dominant- negative receptors for inhibitory cytokines to compensate for an immunosuppressive tumor milieu. In addition, suicide genes can install a 'safety switch' on adoptively transferred cells to allow ablation if necessary. Although further refinement and validation are necessary, these genetic modification strategies offer hope for significant improvements in cancer immunotherapy.
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