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

• Published in: Nature communications Vol. 10; no. 1; p. 449
• Main Authors: Cafri, Gal, Yossef, Rami, Pasetto, Anna, Deniger, Drew C., Lu, Yong-Chen, Parkhurst, Maria, Gartner, Jared J., Jia, Li, Ray, Satyajit, Ngo, Lien T., Jafferji, Mohammad, Sachs, Abraham, Prickett, Todd, Robbins, Paul F., Rosenberg, Steven A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.01.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/109; 13/31; 45/23; 45/91; 49; 631/250; 631/67/1059/2325; Antigen Presentation; Blood; Cancer; Cancer immunotherapy; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - pathology; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - pathology; Cell Separation - methods; Coculture Techniques; Colon; Colon cancer; Colonic Neoplasms - genetics; Colonic Neoplasms - immunology; Colonic Neoplasms - pathology; Dendritic Cells - cytology; Dendritic Cells - immunology; Gene Expression Regulation, Neoplastic; Humanities and Social Sciences; Humans; Immunologic Memory; Immunological memory; Immunotherapy; Lymphatic Metastasis; Lymphocyte Activation; Lymphocytes; Lymphocytes T; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - pathology; Memory cells; Metastases; Metastasis; Molecular Targeted Therapy; Mucin-4 - genetics; Mucin-4 - immunology; multidisciplinary; Mutation; Neoantigens; Neoplastic Cells, Circulating - immunology; Neoplastic Cells, Circulating - pathology; Patients; Peripheral blood; Proteins; Proto-Oncogene Proteins p21(ras) - genetics; Proto-Oncogene Proteins p21(ras) - immunology; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - immunology; Science; Science (multidisciplinary); Signal Transduction; Smad5 protein; Smad5 Protein - genetics; Smad5 Protein - immunology; Transduction, Genetic; Tumors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-08304-z

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 KRAS G12D and KRAS G12V 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. Adoptive cell therapy (ACT) using neoantigen-specific T cells can lead to tumor regression. Here the authors use an in vitro stimulation approach to isolate tumor specific memory T cells from peripheral blood of metastatic epithelial cancer patients targeting unique as well as shared mutations in the KRAS oncogene.