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

Gal Cafri, Rami Yossef, Anna Pasetto, Drew C. Deniger, Yong-Chen Lu, Maria Parkhurst, Jared J. Gartner, Li Jia, Satyajit Ray, Lien T. Ngo, Mohammad Jafferji, Abraham Sachs, Todd Prickett, Paul F. Robbins and Steven A. Rosenberg ()
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Gal Cafri: National Institutes of Health
Rami Yossef: National Institutes of Health
Anna Pasetto: National Institutes of Health
Drew C. Deniger: National Institutes of Health
Yong-Chen Lu: National Institutes of Health
Maria Parkhurst: National Institutes of Health
Jared J. Gartner: National Institutes of Health
Li Jia: National Institutes of Health
Satyajit Ray: National Institutes of Health
Lien T. Ngo: National Institutes of Health
Mohammad Jafferji: National Institutes of Health
Abraham Sachs: National Institutes of Health
Todd Prickett: National Institutes of Health
Paul F. Robbins: National Institutes of Health
Steven A. Rosenberg: National Institutes of Health

Nature Communications, 2019, vol. 10, issue 1, 1-9

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-08304-z

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