Use of CAR-Transduced Natural Killer Cells in CD19-Positive Lymphoid Tumors
Enli LiuFrom the Departments of Stem Cell Transplantation and Cellular Therapy (E.L., D.M., P.B., R.B., L.N.K., B.O., M. Kaplan, V.N., I.K., A.N.C., M.D., C.H., P.K., R.M., Y.N., R.C., E.J.S., K.R.), Nuclear Medicine (H.A.M.), Leukemia (P. Thompson, W.W., M. Keating), Biostatistics (P. Thall), Laboratory Medicine (K.C.), Hematopathology (E.N.C.), and Lymphoma and Myeloma (S.N., M.W.), University of Texas M.D. Anderson Cancer Center, HoustonDavid MarínFrom the Departments of Stem Cell Transplantation and Cellular Therapy (E.L., D.M., P.B., R.B., L.N.K., B.O., M. Kaplan, V.N., I.K., A.N.C., M.D., C.H., P.K., R.M., Y.N., R.C., E.J.S., K.R.), Nuclear Medicine (H.A.M.), Leukemia (P. Thompson, W.W., M. Keating), Biostatistics (P. Thall), Laboratory Medicine (K.C.), Hematopathology (E.N.C.), and Lymphoma and Myeloma (S.N., M.W.), University of Texas M.D. Anderson Cancer Center, HoustonPinaki P. BanerjeeFrom the Departments of Stem Cell Transplantation and Cellular Therapy (E.L., D.M., P.B., R.B., L.N.K., B.O., M. Kaplan, V.N., I.K., A.N.C., M.D., C.H., P.K., R.M., Y.N., R.C., E.J.S., K.R.), Nuclear Medicine (H.A.M.), Leukemia (P. Thompson, W.W., M. Keating), Biostatistics (P. Thall), Laboratory Medicine (K.C.), Hematopathology (E.N.C.), and Lymphoma and Myeloma (S.N., M.W.), University of Texas M.D. Anderson Cancer Center, HoustonHomer A. MacapinlacFrom the Departments of Stem Cell Transplantation and Cellular Therapy (E.L., D.M., P.B., R.B., L.N.K., B.O., M. Kaplan, V.N., I.K., A.N.C., M.D., C.H., P.K., R.M., Y.N., R.C., E.J.S., K.R.), Nuclear Medicine (H.A.M.), Leukemia (P. Thompson, W.W., M. Keating), Biostatistics (P. Thall), Laboratory Medicine (K.C.), Hematopathology (E.N.C.), and Lymphoma and Myeloma (S.N., M.W.), University of Texas M.D. Anderson Cancer Center, HoustonPhilip A. ThompsonFrom the Departments of Stem Cell Transplantation and Cellular Therapy (E.L., D.M., P.B., R.B., L.N.K., B.O., M. Kaplan, V.N., I.K., A.N.C., M.D., C.H., P.K., R.M., Y.N., R.C., E.J.S., K.R.), Nuclear Medicine (H.A.M.), Leukemia (P. Thompson, W.W., M. Keating), Biostatistics (P. Thall), Laboratory Medicine (K.C.), Hematopathology (E.N.C.), and Lymphoma and Myeloma (S.N., M.W.), University of Texas M.D. Anderson Cancer Center, HoustonRafet BaşarFrom the Departments of Stem Cell Transplantation and Cellular Therapy (E.L., D.M., P.B., R.B., L.N.K., B.O., M. Kaplan, V.N., I.K., A.N.C., M.D., C.H., P.K., R.M., Y.N., R.C., E.J.S., K.R.), Nuclear Medicine (H.A.M.), Leukemia (P. Thompson, W.W., M. Keating), Biostatistics (P. Thall), Laboratory Medicine (K.C.), Hematopathology (E.N.C.), and Lymphoma and Myeloma (S.N., M.W.), University of Texas M.D. Anderson Cancer Center, HoustonLucila Nassif KerbauyFrom the Departments of Stem Cell Transplantation and Cellular Therapy (E.L., D.M., P.B., R.B., L.N.K., B.O., M. Kaplan, V.N., I.K., A.N.C., M.D., C.H., P.K., R.M., Y.N., R.C., E.J.S., K.R.), Nuclear Medicine (H.A.M.), Leukemia (P. Thompson, W.W., M. Keating), Biostatistics (P. Thall), Laboratory Medicine (K.C.), Hematopathology (E.N.C.), and Lymphoma and Myeloma (S.N., M.W.), University of Texas M.D. Anderson Cancer Center, HoustonBethany OvermanFrom the Departments of Stem Cell Transplantation and Cellular Therapy (E.L., D.M., P.B., R.B., L.N.K., B.O., M. Kaplan, V.N., I.K., A.N.C., M.D., C.H., P.K., R.M., Y.N., R.C., E.J.S., K.R.), Nuclear Medicine (H.A.M.), Leukemia (P. Thompson, W.W., M. Keating), Biostatistics (P. Thall), Laboratory Medicine (K.C.), Hematopathology (E.N.C.), and Lymphoma and Myeloma (S.N., M.W.), University of Texas M.D. Anderson Cancer Center, HoustonPeter F. ThallFrom the Departments of Stem Cell Transplantation and Cellular Therapy (E.L., D.M., P.B., R.B., L.N.K., B.O., M. Kaplan, V.N., I.K., A.N.C., M.D., C.H., P.K., R.M., Y.N., R.C., E.J.S., K.R.), Nuclear Medicine (H.A.M.), Leukemia (P. Thompson, W.W., M. Keating), Biostatistics (P. Thall), Laboratory Medicine (K.C.), Hematopathology (E.N.C.), and Lymphoma and Myeloma (S.N., M.W.), University of Texas M.D. Anderson Cancer Center, HoustonMecit KaplanFrom the Departments of Stem Cell Transplantation and Cellular Therapy (E.L., D.M., P.B., R.B., L.N.K., B.O., M. Kaplan, V.N., I.K., A.N.C., M.D., C.H., P.K., R.M., Y.N., R.C., E.J.S., K.R.), Nuclear Medicine (H.A.M.), Leukemia (P. Thompson, W.W., M. Keating), Biostatistics (P. Thall), Laboratory Medicine (K.C.), Hematopathology (E.N.C.), and Lymphoma and Myeloma (S.N., M.W.), University of Texas M.D. Anderson Cancer Center, HoustonVandana NandivadaFrom the Departments of Stem Cell Transplantation and Cellular Therapy (E.L., D.M., P.B., R.B., L.N.K., B.O., M. Kaplan, V.N., I.K., A.N.C., M.D., C.H., P.K., R.M., Y.N., R.C., E.J.S., K.R.), Nuclear Medicine (H.A.M.), Leukemia (P. Thompson, W.W., M. Keating), Biostatistics (P. Thall), Laboratory Medicine (K.C.), Hematopathology (E.N.C.), and Lymphoma and Myeloma (S.N., M.W.), University of Texas M.D. Anderson Cancer Center, HoustonIndresh KaurFrom the Departments of Stem Cell Transplantation and Cellular Therapy (E.L., D.M., P.B., R.B., L.N.K., B.O., M. Kaplan, V.N., I.K., A.N.C., M.D., C.H., P.K., R.M., Y.N., R.C., E.J.S., K.R.), Nuclear Medicine (H.A.M.), Leukemia (P. Thompson, W.W., M. Keating), Biostatistics (P. Thall), Laboratory Medicine (K.C.), Hematopathology (E.N.C.), and Lymphoma and Myeloma (S.N., M.W.), University of Texas M.D. Anderson Cancer Center, HoustonAna Karen Nunez CortesFrom the Departments of Stem Cell Transplantation and Cellular Therapy (E.L., D.M., P.B., R.B., L.N.K., B.O., M. Kaplan, V.N., I.K., A.N.C., M.D., C.H., P.K., R.M., Y.N., R.C., E.J.S., K.R.), Nuclear Medicine (H.A.M.), Leukemia (P. Thompson, W.W., M. Keating), Biostatistics (P. Thall), Laboratory Medicine (K.C.), Hematopathology (E.N.C.), and Lymphoma and Myeloma (S.N., M.W.), University of Texas M.D. Anderson Cancer Center, HoustonKai CaoFrom the Departments of Stem Cell Transplantation and Cellular Therapy (E.L., D.M., P.B., R.B., L.N.K., B.O., M. Kaplan, V.N., I.K., A.N.C., M.D., C.H., P.K., R.M., Y.N., R.C., E.J.S., K.R.), Nuclear Medicine (H.A.M.), Leukemia (P. Thompson, W.W., M. Keating), Biostatistics (P. Thall), Laboratory Medicine (K.C.), Hematopathology (E.N.C.), and Lymphoma and Myeloma (S.N., M.W.), University of Texas M.D. Anderson Cancer Center, HoustonMay DaherFrom the Departments of Stem Cell Transplantation and Cellular Therapy (E.L., D.M., P.B., R.B., L.N.K., B.O., M. Kaplan, V.N., I.K., A.N.C., M.D., C.H., P.K., R.M., Y.N., R.C., E.J.S., K.R.), Nuclear Medicine (H.A.M.), Leukemia (P. Thompson, W.W., M. Keating), Biostatistics (P. Thall), Laboratory Medicine (K.C.), Hematopathology (E.N.C.), and Lymphoma and Myeloma (S.N., M.W.), University of Texas M.D. Anderson Cancer Center, HoustonChitra HosingFrom the Departments of Stem Cell Transplantation and Cellular Therapy (E.L., D.M., P.B., R.B., L.N.K., B.O., M. Kaplan, V.N., I.K., A.N.C., M.D., C.H., P.K., R.M., Y.N., R.C., E.J.S., K.R.), Nuclear Medicine (H.A.M.), Leukemia (P. Thompson, W.W., M. Keating), Biostatistics (P. Thall), Laboratory Medicine (K.C.), Hematopathology (E.N.C.), and Lymphoma and Myeloma (S.N., M.W.), University of Texas M.D. Anderson Cancer Center, HoustonEvan N. CohenFrom the Departments of Stem Cell Transplantation and Cellular Therapy (E.L., D.M., P.B., R.B., L.N.K., B.O., M. Kaplan, V.N., I.K., A.N.C., M.D., C.H., P.K., R.M., Y.N., R.C., E.J.S., K.R.), Nuclear Medicine (H.A.M.), Leukemia (P. Thompson, W.W., M. Keating), Biostatistics (P. Thall), Laboratory Medicine (K.C.), Hematopathology (E.N.C.), and Lymphoma and Myeloma (S.N., M.W.), University of Texas M.D. Anderson Cancer Center, HoustonPartow KebriaeiFrom the Departments of Stem Cell Transplantation and Cellular Therapy (E.L., D.M., P.B., R.B., L.N.K., B.O., M. Kaplan, V.N., I.K., A.N.C., M.D., C.H., P.K., R.M., Y.N., R.C., E.J.S., K.R.), Nuclear Medicine (H.A.M.), Leukemia (P. Thompson, W.W., M. Keating), Biostatistics (P. Thall), Laboratory Medicine (K.C.), Hematopathology (E.N.C.), and Lymphoma and Myeloma (S.N., M.W.), University of Texas M.D. Anderson Cancer Center, HoustonRohtesh S. MehtaFrom the Departments of Stem Cell Transplantation and Cellular Therapy (E.L., D.M., P.B., R.B., L.N.K., B.O., M. Kaplan, V.N., I.K., A.N.C., M.D., C.H., P.K., R.M., Y.N., R.C., E.J.S., K.R.), Nuclear Medicine (H.A.M.), Leukemia (P. Thompson, W.W., M. Keating), Biostatistics (P. Thall), Laboratory Medicine (K.C.), Hematopathology (E.N.C.), and Lymphoma and Myeloma (S.N., M.W.), University of Texas M.D. Anderson Cancer Center, HoustonSattva S. NeelapuFrom the Departments of Stem Cell Transplantation and Cellular Therapy (E.L., D.M., P.B., R.B., L.N.K., B.O., M. Kaplan, V.N., I.K., A.N.C., M.D., C.H., P.K., R.M., Y.N., R.C., E.J.S., K.R.), Nuclear Medicine (H.A.M.), Leukemia (P. Thompson, W.W., M. Keating), Biostatistics (P. Thall), Laboratory Medicine (K.C.), Hematopathology (E.N.C.), and Lymphoma and Myeloma (S.N., M.W.), University of Texas M.D. Anderson Cancer Center, HoustonYago NietoFrom the Departments of Stem Cell Transplantation and Cellular Therapy (E.L., D.M., P.B., R.B., L.N.K., B.O., M. Kaplan, V.N., I.K., A.N.C., M.D., C.H., P.K., R.M., Y.N., R.C., E.J.S., K.R.), Nuclear Medicine (H.A.M.), Leukemia (P. Thompson, W.W., M. Keating), Biostatistics (P. Thall), Laboratory Medicine (K.C.), Hematopathology (E.N.C.), and Lymphoma and Myeloma (S.N., M.W.), University of Texas M.D. Anderson Cancer Center, HoustonMichael WangFrom the Departments of Stem Cell Transplantation and Cellular Therapy (E.L., D.M., P.B., R.B., L.N.K., B.O., M. Kaplan, V.N., I.K., A.N.C., M.D., C.H., P.K., R.M., Y.N., R.C., E.J.S., K.R.), Nuclear Medicine (H.A.M.), Leukemia (P. Thompson, W.W., M. Keating), Biostatistics (P. Thall), Laboratory Medicine (K.C.), Hematopathology (E.N.C.), and Lymphoma and Myeloma (S.N., M.W.), University of Texas M.D. Anderson Cancer Center, HoustonWilliam G. WierdaFrom the Departments of Stem Cell Transplantation and Cellular Therapy (E.L., D.M., P.B., R.B., L.N.K., B.O., M. Kaplan, V.N., I.K., A.N.C., M.D., C.H., P.K., R.M., Y.N., R.C., E.J.S., K.R.), Nuclear Medicine (H.A.M.), Leukemia (P. Thompson, W.W., M. Keating), Biostatistics (P. Thall), Laboratory Medicine (K.C.), Hematopathology (E.N.C.), and Lymphoma and Myeloma (S.N., M.W.), University of Texas M.D. Anderson Cancer Center, HoustonMichael J. KeatingFrom the Departments of Stem Cell Transplantation and Cellular Therapy (E.L., D.M., P.B., R.B., L.N.K., B.O., M. Kaplan, V.N., I.K., A.N.C., M.D., C.H., P.K., R.M., Y.N., R.C., E.J.S., K.R.), Nuclear Medicine (H.A.M.), Leukemia (P. Thompson, W.W., M. Keating), Biostatistics (P. Thall), Laboratory Medicine (K.C.), Hematopathology (E.N.C.), and Lymphoma and Myeloma (S.N., M.W.), University of Texas M.D. Anderson Cancer Center, HoustonRichard E. ChamplinFrom the Departments of Stem Cell Transplantation and Cellular Therapy (E.L., D.M., P.B., R.B., L.N.K., B.O., M. Kaplan, V.N., I.K., A.N.C., M.D., C.H., P.K., R.M., Y.N., R.C., E.J.S., K.R.), Nuclear Medicine (H.A.M.), Leukemia (P. Thompson, W.W., M. Keating), Biostatistics (P. Thall), Laboratory Medicine (K.C.), Hematopathology (E.N.C.), and Lymphoma and Myeloma (S.N., M.W.), University of Texas M.D. Anderson Cancer Center, HoustonElizabeth J. ShpallFrom the Departments of Stem Cell Transplantation and Cellular Therapy (E.L., D.M., P.B., R.B., L.N.K., B.O., M. Kaplan, V.N., I.K., A.N.C., M.D., C.H., P.K., R.M., Y.N., R.C., E.J.S., K.R.), Nuclear Medicine (H.A.M.), Leukemia (P. Thompson, W.W., M. Keating), Biostatistics (P. Thall), Laboratory Medicine (K.C.), Hematopathology (E.N.C.), and Lymphoma and Myeloma (S.N., M.W.), University of Texas M.D. Anderson Cancer Center, HoustonKatayoun RezvaniFrom the Departments of Stem Cell Transplantation and Cellular Therapy (E.L., D.M., P.B., R.B., L.N.K., B.O., M. Kaplan, V.N., I.K., A.N.C., M.D., C.H., P.K., R.M., Y.N., R.C., E.J.S., K.R.), Nuclear Medicine (H.A.M.), Leukemia (P. Thompson, W.W., M. Keating), Biostatistics (P. Thall), Laboratory Medicine (K.C.), Hematopathology (E.N.C.), and Lymphoma and Myeloma (S.N., M.W.), University of Texas M.D. Anderson Cancer Center, Houston
2020en
ABI
Аннотация
BACKGROUND: Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has shown remarkable clinical efficacy in B-cell cancers. However, CAR T cells can induce substantial toxic effects, and the manufacture of the cells is complex. Natural killer (NK) cells that have been modified to express an anti-CD19 CAR have the potential to overcome these limitations. METHODS: CAR-NK cells per kilogram of body weight) after lymphodepleting chemotherapy. RESULTS: The administration of CAR-NK cells was not associated with the development of cytokine release syndrome, neurotoxicity, or graft-versus-host disease, and there was no increase in the levels of inflammatory cytokines, including interleukin-6, over baseline. The maximum tolerated dose was not reached. Of the 11 patients who were treated, 8 (73%) had a response; of these patients, 7 (4 with lymphoma and 3 with CLL) had a complete remission, and 1 had remission of the Richter's transformation component but had persistent CLL. Responses were rapid and seen within 30 days after infusion at all dose levels. The infused CAR-NK cells expanded and persisted at low levels for at least 12 months. CONCLUSIONS: Among 11 patients with relapsed or refractory CD19-positive cancers, a majority had a response to treatment with CAR-NK cells without the development of major toxic effects. (Funded by the M.D. Anderson Cancer Center CLL and Lymphoma Moonshot and the National Institutes of Health; ClinicalTrials.gov number, NCT03056339.).
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