Cancer Immunotherapy Based on Mutation-Specific CD4+ T Cells in a Patient with Epithelial Cancer

作者：Eric Tran, Simon Turcotte, Alena Gros, Paul F. Robbins, Yong‐Chen Lu, Mark E. Dudley, John R. Wunderlich, Robert Somerville, Katherine Hogan, Christian S. Hinrichs, Maria R. Parkhurst, James C. Yang, Steven A. Rosenberg · 发表于：Science · 年份：2014 · DOI：10.1126/science.1251102 · 被引用次数：1734 · 研究领域：CAR-T cell therapy research、Immunotherapy and Immune Responses、Cancer Immunotherapy and Biomarkers

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.