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Science. 2014 May 9;344(6184):641-5. doi: 10.1126/science.1251102.

Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer.

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  • 1Surgery Branch, National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD 20892, USA.

Abstract

Limited evidence exists that humans mount a mutation-specific T cell response to epithelial cancers. We used a whole-exomic-sequencing-based approach to demonstrate that tumor-infiltrating lymphocytes (TIL) from a patient with metastatic cholangiocarcinoma contained CD4+ T helper 1 (T(H)1) cells recognizing a mutation in erbb2 interacting protein (ERBB2IP) expressed by the cancer. After adoptive transfer of TIL containing about 25% mutation-specific polyfunctional T(H)1 cells, the patient achieved a decrease in target lesions with prolonged stabilization of disease. Upon disease progression, the patient was retreated with a >95% pure population of mutation-reactive T(H)1 cells and again experienced tumor regression. These results provide evidence that a CD4+ T cell response against a mutated antigen can be harnessed to mediate regression of a metastatic epithelial cancer.

PMID:
24812403
[PubMed - indexed for MEDLINE]
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