Publication Date:
2014-05-09
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tran, Eric -- Turcotte, Simon -- Gros, Alena -- Robbins, Paul F -- Lu, Yong-Chen -- Dudley, Mark E -- Wunderlich, John R -- Somerville, Robert P -- Hogan, Katherine -- Hinrichs, Christian S -- Parkhurst, Maria R -- Yang, James C -- Rosenberg, Steven A -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2014 May 9;344(6184):641-5. doi: 10.1126/science.1251102.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Surgery Branch, National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24812403" target="_blank"〉PubMed〈/a〉
Keywords:
Adaptor Proteins, Signal Transducing/*genetics
;
Adoptive Transfer/*methods
;
Adult
;
Bile Duct Neoplasms/genetics/*therapy
;
*Bile Ducts, Intrahepatic
;
CD4-Positive T-Lymphocytes/*immunology
;
Cholangiocarcinoma/genetics/*therapy
;
Clinical Trials, Phase II as Topic
;
Exome
;
Female
;
Humans
;
Lymphocytes, Tumor-Infiltrating/*transplantation
;
Mutation
;
Receptor, ErbB-2/metabolism
;
Th1 Cells/*transplantation
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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