Neoantigen T-Cell Receptor Gene Therapy in Pancreatic Cancer.

Autor:	Leidner R; From the Earle A. Chiles Research Institute (R.L., N.S.S., H.H., D.S., C.Z., Y.-P.S., A.L., B.A.F., W.J.U., E.T.), Providence Cancer Institute (R.L., N.S.S., H.H., D.S., C.Z., Y.-P.S., A.L., R.P., K.S., J.C., B.A.F., W.J.U., E.T.), Portland, OR; and the Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD (S.A.R.)., Sanjuan Silva N; From the Earle A. Chiles Research Institute (R.L., N.S.S., H.H., D.S., C.Z., Y.-P.S., A.L., B.A.F., W.J.U., E.T.), Providence Cancer Institute (R.L., N.S.S., H.H., D.S., C.Z., Y.-P.S., A.L., R.P., K.S., J.C., B.A.F., W.J.U., E.T.), Portland, OR; and the Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD (S.A.R.)., Huang H; From the Earle A. Chiles Research Institute (R.L., N.S.S., H.H., D.S., C.Z., Y.-P.S., A.L., B.A.F., W.J.U., E.T.), Providence Cancer Institute (R.L., N.S.S., H.H., D.S., C.Z., Y.-P.S., A.L., R.P., K.S., J.C., B.A.F., W.J.U., E.T.), Portland, OR; and the Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD (S.A.R.)., Sprott D; From the Earle A. Chiles Research Institute (R.L., N.S.S., H.H., D.S., C.Z., Y.-P.S., A.L., B.A.F., W.J.U., E.T.), Providence Cancer Institute (R.L., N.S.S., H.H., D.S., C.Z., Y.-P.S., A.L., R.P., K.S., J.C., B.A.F., W.J.U., E.T.), Portland, OR; and the Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD (S.A.R.)., Zheng C; From the Earle A. Chiles Research Institute (R.L., N.S.S., H.H., D.S., C.Z., Y.-P.S., A.L., B.A.F., W.J.U., E.T.), Providence Cancer Institute (R.L., N.S.S., H.H., D.S., C.Z., Y.-P.S., A.L., R.P., K.S., J.C., B.A.F., W.J.U., E.T.), Portland, OR; and the Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD (S.A.R.)., Shih YP; From the Earle A. Chiles Research Institute (R.L., N.S.S., H.H., D.S., C.Z., Y.-P.S., A.L., B.A.F., W.J.U., E.T.), Providence Cancer Institute (R.L., N.S.S., H.H., D.S., C.Z., Y.-P.S., A.L., R.P., K.S., J.C., B.A.F., W.J.U., E.T.), Portland, OR; and the Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD (S.A.R.)., Leung A; From the Earle A. Chiles Research Institute (R.L., N.S.S., H.H., D.S., C.Z., Y.-P.S., A.L., B.A.F., W.J.U., E.T.), Providence Cancer Institute (R.L., N.S.S., H.H., D.S., C.Z., Y.-P.S., A.L., R.P., K.S., J.C., B.A.F., W.J.U., E.T.), Portland, OR; and the Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD (S.A.R.)., Payne R; From the Earle A. Chiles Research Institute (R.L., N.S.S., H.H., D.S., C.Z., Y.-P.S., A.L., B.A.F., W.J.U., E.T.), Providence Cancer Institute (R.L., N.S.S., H.H., D.S., C.Z., Y.-P.S., A.L., R.P., K.S., J.C., B.A.F., W.J.U., E.T.), Portland, OR; and the Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD (S.A.R.)., Sutcliffe K; From the Earle A. Chiles Research Institute (R.L., N.S.S., H.H., D.S., C.Z., Y.-P.S., A.L., B.A.F., W.J.U., E.T.), Providence Cancer Institute (R.L., N.S.S., H.H., D.S., C.Z., Y.-P.S., A.L., R.P., K.S., J.C., B.A.F., W.J.U., E.T.), Portland, OR; and the Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD (S.A.R.)., Cramer J; From the Earle A. Chiles Research Institute (R.L., N.S.S., H.H., D.S., C.Z., Y.-P.S., A.L., B.A.F., W.J.U., E.T.), Providence Cancer Institute (R.L., N.S.S., H.H., D.S., C.Z., Y.-P.S., A.L., R.P., K.S., J.C., B.A.F., W.J.U., E.T.), Portland, OR; and the Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD (S.A.R.)., Rosenberg SA; From the Earle A. Chiles Research Institute (R.L., N.S.S., H.H., D.S., C.Z., Y.-P.S., A.L., B.A.F., W.J.U., E.T.), Providence Cancer Institute (R.L., N.S.S., H.H., D.S., C.Z., Y.-P.S., A.L., R.P., K.S., J.C., B.A.F., W.J.U., E.T.), Portland, OR; and the Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD (S.A.R.)., Fox BA; From the Earle A. Chiles Research Institute (R.L., N.S.S., H.H., D.S., C.Z., Y.-P.S., A.L., B.A.F., W.J.U., E.T.), Providence Cancer Institute (R.L., N.S.S., H.H., D.S., C.Z., Y.-P.S., A.L., R.P., K.S., J.C., B.A.F., W.J.U., E.T.), Portland, OR; and the Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD (S.A.R.)., Urba WJ; From the Earle A. Chiles Research Institute (R.L., N.S.S., H.H., D.S., C.Z., Y.-P.S., A.L., B.A.F., W.J.U., E.T.), Providence Cancer Institute (R.L., N.S.S., H.H., D.S., C.Z., Y.-P.S., A.L., R.P., K.S., J.C., B.A.F., W.J.U., E.T.), Portland, OR; and the Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD (S.A.R.)., Tran E; From the Earle A. Chiles Research Institute (R.L., N.S.S., H.H., D.S., C.Z., Y.-P.S., A.L., B.A.F., W.J.U., E.T.), Providence Cancer Institute (R.L., N.S.S., H.H., D.S., C.Z., Y.-P.S., A.L., R.P., K.S., J.C., B.A.F., W.J.U., E.T.), Portland, OR; and the Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD (S.A.R.).
Jazyk:	angličtina
Zdroj:	The New England journal of medicine [N Engl J Med] 2022 Jun 02; Vol. 386 (22), pp. 2112-2119.
DOI:	10.1056/NEJMoa2119662
Abstrakt:	A patient with progressive metastatic pancreatic cancer was treated with a single infusion of 16.2×10 9 autologous T cells that had been genetically engineered to clonally express two allogeneic HLA-C*08:02-restricted T-cell receptors (TCRs) targeting mutant KRAS G12D expressed by the tumors. The patient had regression of visceral metastases (overall partial response of 72% according to the Response Evaluation Criteria in Solid Tumors, version 1.1); the response was ongoing at 6 months. The engineered T cells constituted more than 2% of all the circulating peripheral-blood T cells 6 months after the cell transfer. In this patient, TCR gene therapy targeting the KRAS G12D driver mutation mediated the objective regression of metastatic pancreatic cancer. (Funded by the Providence Portland Medical Foundation.). (Copyright © 2022 Massachusetts Medical Society.)
Databáze:	MEDLINE
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