title: Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer.
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.
authors.affiliation: Surgery Branch, National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Tran
authors.forename: Simon
authors.initials: S
authors.lastname: Turcotte
authors.forename: Alena
authors.initials: A
authors.lastname: Gros
authors.forename: Paul F
authors.initials: PF
authors.lastname: Robbins
authors.forename: Yong-Chen
authors.initials: YC
authors.lastname: Lu
authors.forename: Mark E
authors.initials: ME
authors.lastname: Dudley
authors.forename: John R
authors.initials: JR
authors.lastname: Wunderlich
authors.forename: Robert P
authors.initials: RP
authors.lastname: Somerville
authors.forename: Katherine
authors.initials: K
authors.lastname: Hogan
authors.forename: Christian S
authors.initials: CS
authors.lastname: Hinrichs
authors.forename: Maria R
authors.initials: MR
authors.lastname: Parkhurst
authors.forename: James C
authors.initials: JC
authors.lastname: Yang
authors.forename: Steven A
authors.initials: SA
authors.lastname: Rosenberg
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D019264:Adoptive Transfer / Q000379:methods*; D000328:Adult; D001650:Bile Duct Neoplasms / Q000235:genetics / Q000628:therapy*; D001653:Bile Ducts, Intrahepatic; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018281:Cholangiocarcinoma / Q000235:genetics / Q000628:therapy*; D017322:Clinical Trials, Phase II as Topic; D059472:Exome; D005260:Female; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000637:transplantation*; D009154:Mutation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D018417:Th1 Cells / Q000637:transplantation*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018719:Erb-b2 Receptor Tyrosine Kinases; C413364:ERBIN protein, human