Journal
CURRENT OPINION IN IMMUNOLOGY
Volume 51, Issue -, Pages 103-110Publisher
CURRENT BIOLOGY LTD
DOI: 10.1016/j.coi.2018.03.002
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Funding
- National Institutes of Health [P30 CA008748]
- U.S. Department of Defense [BC132124, LC160212]
- Derfner Foundation
- Joanne and John DallePezze Foundation
- Commonwealth Foundation for Cancer Research
- Experimental Therapeutics Center of Memorial Sloan Kettering Cancer Center
- NATIONAL CANCER INSTITUTE [P30CA008748, T32CA009501] Funding Source: NIH RePORTER
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Uniform and strong expression of CD19, a cell surface antigen, on cells of B-cell lineage is unique to hematologic malignancies. Tumor-associated antigen (TAA) targets in solid tumors exhibit heterogeneity with regards to intensity and distribution, posing a challenge for chimeric antigen receptor (CAR) T-cell therapy. Novel CAR designs, such as dual TAA-targeted CARs, tandem CARs, and switchable CARs, in conjunction with inhibitory CARs, are being investigated as means to overcome antigen heterogeneity. In addition to heterogeneity in cancer-cell antigen expression, the key determinants for antitumor responses are CAR expression levels and affinity in T cells. Herein, we review CAR T-cell therapy clinical trials for patients with lung or pancreatic cancers, and provide detailed translational strategies to overcome antigen heterogeneity.
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