Journal
JOURNAL OF IMMUNOLOGY
Volume 200, Issue 2, Pages 459-468Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1701155
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Funding
- National Institutes of Health [CA136551, CA114536]
- Cancer Research Institute Irvington Postdoctoral Fellowship
- NATIONAL CANCER INSTITUTE [R01CA136551, R01CA114536] Funding Source: NIH RePORTER
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Immunotherapy with T cells genetically modified to express chimeric Ag receptors (CARs) that target tumor-associated molecules have impressive efficacy in hematological malignancies. The field has now embraced the challenge of applying this approach to treat common epithelial malignancies, which make up the majority of cancer cases but evade immunologic attack by a variety of subversive mechanisms. In this study, we review the principles that have guided CAR T cell design and the extraordinary clinical results being achieved in B cell malignancies targeting CD19 with a single infusion of engineered T cells. This success has raised expectations that CAR T cells can be applied to solid tumors, but numerous obstacles must be overcome to achieve the success observed in hematologic cancers. Potential solutions driven by advances in genetic engineering, synthetic biology, T cell biology, and improved tumor models that recapitulate the obstacles in human tumors are discussed.
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