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

Eric Tran1, Simon Turcotte1,*, Alena Gros1, Paul F. Robbins1, Yong-Chen Lu1, Mark E. Dudley1,†, John R. Wunderlich1, Robert P. Somerville1, Katherine Hogan1, Christian S. Hinrichs1, Maria R. Parkhurst1, James C. Yang1, Steven A. Rosenberg1,‡
2014-05-09

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 (TH1) cells recognizing a mutation in erbb2 interacting protein (ERBB2IP) expressed by the cancer. After adoptive transfer of TIL containing about 25% mutation-specific polyfunctional TH1 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 TH1 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….

You may also like...