Cancer immunotherapy: Targeting the difference

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 tumour-infiltrating lymphocytes (TILs) from a patient with metastatic cholangiocarcinoma contained CD4+ T helper 1 (TH1) cells, recognizing a mutation in the erbb2 interacting protein (ERBB2IP) expressed by the cancer. After adoptive transfer of TILs, containing about 25% mutation-specific polyfunctional TH1 cells, the patient achieved a decrease in target lesions with prolonged stabilization of the disease. Upon disease progression, the patient was retreated with a >95% pure population of mutation-reactive TH1 cells and again experienced tumour 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.