Cafri et al. developed a highly sensitive method to isolate rare neoantigen-specific T cells based on in vitro stimulation of memory CD8+ T cells from the peripheral blood of two metastatic colon cancer patients. The researchers used this approach to identify CD8+ T cells (A*11:01 restricted) reactive against KRASG12V in a patient with endometrial cancer, and CD4+ T cells (DRB1*08:01 restricted) reactive against KRASG12D in two patients with either rectal or colon cancer. TCRs isolated from T cells reactive to common oncogenic mutations restricted by common HLA alleles may be widely utilized in off-the-shelf treatments.
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.
Author Info: (1) Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. (2) Surgery Branch, National Cancer Institute, National Institutes of Health
Author Info: (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. (3) Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. (4) Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. (5) Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. (6) Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. (7) Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. (8) Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. (9) Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. (10) Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. (11) Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. (12) Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. (13) Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. (14) Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. (15) Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. sar@nih.gov.
