@article{oai:shiga-med.repo.nii.ac.jp:00004082, author = {寺田, 晃士 and 近藤, 健太 and 石垣, 宏仁 and 里岡, 大樹 and 平田, 多佳子 and 小笠原, 一誠 and 伊藤, 靖 and 縣, 保年 and TERADA, Koji and KONDO, Kenta and ISHIGAKI, Hirohito and NAGASHIMA, Ayaka and SATOOKA, Hiroki and NAGANO, Seiji and MASUDA, Kyoko and KAWAMURA, Teruhisa and HIRATA, Takako and OGASAWARA, Kazumasa and ITOH, Yasushi and KAWAMOTO, Hiroshi and AGATA, Yasutoshi}, journal = {Molecular Therapy - Oncolytics}, month = {Mar}, note = {pdf, To develop effective adoptive cell transfer therapy using T cell receptor (TCR)-engineered T cells, it is critical to isolate tumor-reactive TCRs that have potent anti-tumor activity. In humans, tumor-infiltrating lymphocytes (TILs) have been reported to contain CD8+PD-1+ T cells that express tumor-reactive TCRs. Characterization of tumor reactivity of TILs from non-human primate tumors could improve anti-tumor activity of TCR-engineered T cells in preclinical research. In this study, we sought to isolate TCR genes from CD8+PD-1+ T cells among TILs in a cynomolgus macaque model of tumor transplantation in which the tumors were infiltrated with CD8+ T cells and were eventually rejected. We analyzed the repertoire of TCRα and β pairs obtained from single CD8+PD-1+ T cells in TILs and circulating lymphocytes and identified multiple TCR pairs with high frequency, suggesting that T cells expressing these recurrent TCRs were clonally expanded in response to tumor cells. We further showed that the recurrent TCRs exhibited cytotoxic activity to tumor cells in vitro and potent anti-tumor activity in mice transplanted with tumor cells. These results imply that this tumor transplantation macaque model recapitulates key features of human TILs and can serve as a platform toward preclinical studies of non-human primate tumor models., Journal Article}, pages = {77--86}, title = {Isolation of TCR genes with tumor-killing activity from tumor-infiltrating and circulating lymphocytes in a tumor rejection cynomolgus macaque model}, volume = {24}, year = {2022} }