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Nat Commun. 2019 Jan 25;10(1):449. doi: 10.1038/s41467-019-08304-z.

Memory T cells targeting oncogenic mutations detected in peripheral blood of epithelial cancer patients.

Author information

1
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
2
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. sar@nih.gov.

Abstract

T cells targeting shared oncogenic mutations can induce durable tumor regression in epithelial cancer patients. Such T cells can be detected in tumor infiltrating lymphocytes, but whether such cells can be detected in the peripheral blood of patients with the common metastatic epithelial cancer patients is unknown. Using a highly sensitive in vitro stimulation and cell enrichment of peripheral memory T cells from six metastatic cancer patients, we identified and isolated CD4+, and CD8+ memory T cells targeting the mutated KRASG12D and KRASG12V variants, respectively, in three patients. In an additional two metastatic colon cancer patients, we detected CD8+ neoantigen-specific cells targeting the mutated SMAD5 and MUC4 proteins. Therefore, memory T cells targeting unique as well as shared somatic mutations can be detected in the peripheral blood of epithelial cancer patients and can potentially be used for the development of effective personalized T cell-based cancer immunotherapy across multiple patients.

PMID:
30683863
PMCID:
PMC6347629
DOI:
10.1038/s41467-019-08304-z
[Indexed for MEDLINE]
Free PMC Article

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