Journal
CLINICAL CANCER RESEARCH
Volume 21, Issue 15, Pages 3384-3392Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-14-2675
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Funding
- National Institute of General Medical Sciences of the NIH [T32HL092332, T32GM088129]
- Alliance for Cancer Gene Therapy (ACGT)
- Alex's Lemonade Stand Foundation for Childhood Cancer
- Stand Up To Cancer - St. Baldrick's Pediatric Dream Team Translational Research Grant [SU2C-AACR-DT1113]
- NATIONAL CANCER INSTITUTE [P01CA094237] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [T32HL092332] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM088129] Funding Source: NIH RePORTER
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Primary resistant, recurrent, and relapsed solid tumors are often nonresponsive to conventional antineoplastic therapies. Moreover, in responsive tumors, the therapeutic-to-toxic range of these interventions remains quite narrow, such that side effects of therapy are substantial. Targeted therapies, such as adoptive T-cell transfer, not only spare normal tissues but also use alternative killing mechanisms to which the tumor cells are usually not immune. Adoptive T-cell transfer for solid tumors faces unique challenges because of the inherent heterogeneity of tumor parenchyma, the complexity of the tumor microenvironment, and tumor occurrence in areas with limited therapeutic accessibility. In this review, we examine the recent evolution of various T-cell-based immunotherapeutics, the mechanisms of action behind their antitumor activity, their increasing complexity, and the prospect of building on previous successes in the treatment of solid tumors. (C) 2015 AACR.
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