Successful Immunotherapy With Mutation-Specific CD4-Positive T Cells in Patient With Epithelial Cancer

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There is limited evidence of mutation-specific T-cell response to epithelial cancers. In a study reported in Science, Tran and colleagues used whole-exome sequencing to show that tumor-infiltrating lymphocytes included CD4-positive Th1 cells that recognized a mutation in erbb2 interacting protein (ERBB2IP) expressed by a tumor in a patient with metastatic cholangiocarcinoma.

In the setting of progressive disease, adoptive transfer of tumor-infiltrating lymphocytes containing approximately 25% mutation-specific polyfunctional Th1 cells produced tumor regression at 2 months, with lung and liver lesions reaching a maximum reduction of 30% at 7 months. Disease was stabilized for 13 months after infusion, with subsequent progression observed in the lungs but not the liver.

At progression, the patient was re-treated with a > 95% pure population of mutation-reactive Th1 cells. Treatment again produced tumor regression, which was evident at 1 month and was maintained at the last follow-up at 6 months.

The investigators concluded, “These results provide evidence that a CD4[-positive] T cell response against a mutated antigen can be harnessed to mediate regression of a metastatic epithelial cancer…. The ability to immunologically target unique mutations in cancers can potentially extend highly personalized immunotherapies to patients with epithelial cancers, which account for about 90% of cancer deaths in the United States.” ■

Tran E, et al: Science 344:641-645, 2014.




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