Development of allogeneic HSC-engineered iNKT cells for off-the-shelf cancer immunotherapy.

Autor:	Li YR; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA., Zhou Y; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA., Kim YJ; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA., Zhu Y; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA., Ma F; Department of Molecular, Cell and Developmental Biology, College of Letters and Sciences, University of California, Los Angeles, Los Angeles, CA 90095, USA., Yu J; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA., Wang YC; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA., Chen X; Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089, USA., Li Z; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA., Zeng S; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA., Wang X; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA., Lee D; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA., Ku J; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA., Tsao T; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA., Hardoy C; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA., Huang J; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA., Cheng D; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA., Montel-Hagen A; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA., Seet CS; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA.; Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA., Crooks GM; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA.; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.; Department of Pediatrics, University of California, Los Angeles, Los Angeles, CA 90095, USA., Larson SM; Department of Internal Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA., Sasine JP; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA.; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.; Division of Hematology/Oncology, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA., Wang X; Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA., Pellegrini M; Department of Molecular, Cell and Developmental Biology, College of Letters and Sciences, University of California, Los Angeles, Los Angeles, CA 90095, USA.; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA., Ribas A; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA.; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA.; Parker Institute for Cancer Immunotherapy, University of California, Los Angeles, Los Angeles, CA 90095, USA., Kohn DB; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA.; Division of Hematology/Oncology, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA., Witte O; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA.; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.; Parker Institute for Cancer Immunotherapy, University of California, Los Angeles, Los Angeles, CA 90095, USA.; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA., Wang P; Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089, USA., Yang L; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA.; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Jazyk:	angličtina
Zdroj:	Cell reports. Medicine [Cell Rep Med] 2021 Nov 16; Vol. 2 (11), pp. 100449. Date of Electronic Publication: 2021 Nov 16 (Print Publication: 2021).
DOI:	10.1016/j.xcrm.2021.100449
Abstrakt:	Cell-based immunotherapy has become the new-generation cancer medicine, and "off-the-shelf" cell products that can be manufactured at large scale and distributed readily to treat patients are necessary. Invariant natural killer T (iNKT) cells are ideal cell carriers for developing allogeneic cell therapy because they are powerful immune cells targeting cancers without graft-versus-host disease (GvHD) risk. However, healthy donor blood contains extremely low numbers of endogenous iNKT cells. Here, by combining hematopoietic stem cell (HSC) gene engineering and in vitro differentiation, we generate human allogeneic HSC-engineered iNKT ( Allo HSC-iNKT) cells at high yield and purity; these cells closely resemble endogenous iNKT cells, effectively target tumor cells using multiple mechanisms, and exhibit high safety and low immunogenicity. These cells can be further engineered with chimeric antigen receptor (CAR) to enhance tumor targeting or/and gene edited to ablate surface human leukocyte antigen (HLA) molecules and further reduce immunogenicity. Collectively, these preclinical studies demonstrate the feasibility and cancer therapy potential of Allo HSC-iNKT cell products and lay a foundation for their translational and clinical development. Competing Interests: Y.-R.L., Y.J.K., J.Y., P.W., Y. Zhu, G.M.C., A.M.-H., C.S.S., and L.Y. are inventors on patents relating to this study filed by UCLA. Y.J.K. is currently an employee of Nkarta. J.Y. and X.W. are currently employees of Appia Bio. X.C. is currently an employee of Atara Bio. Z.L. is currently an employee of Allogene. S.M.L. is a stockholder of 1200 Pharma and TORL BioTherapeutics. A.R. is a consultant for Amgen, Bristol-Meyers Squibb, Chugai, Genentech-Roche, Merck-MSD, Novartis, and Sanofi; a scientific advisory board member of and stockholder with Advaxis, Apricity, Arcus, Bioncotech, Compugen, CytomX, Five Prime, FLX-Bio, ImaginAb, Isoplexis, Kite-Gilead, Merus, Rgenix, and Appia Bio; and a co-founder and scientific advisory board member of Lutris, PACT Pharma, and Tango Therapeutics. J.S. is a consultant for Kite and on the speaker bureau for Kite and BMS. D.B.K. is a stockholder and scientific advisory board member of Allogene Therapeutics, Myogene Bio, ImmunoVec and Pluto Therapeutics. O.N.W. currently has consulting, equity, and/or board relationships with Trethera Corporation, Kronos Biosciences, Sofie Biosciences, Breakthrough Properties, Vida Ventures, Nammi Therapeutics, Two River, Iconovir, Appia BioSciences, Neogene Therapeutics, and Allogene Therapeutics. P.W. is a co-founder, stockholder, consultant, and advisory board member of HRain Biotechnology, TCRCure Biopharma, and Appia Bio. G.M.C., C.S.S., and A.M.-H. are cofounders and stockholders of Pluto Immunotherapeutics. L.Y. is a scientific advisor to AlzChem and Amberstone Biosciensec, and a co-founder, stockholder, and advisory board member of Appia Bio. None of the declared companies contributed to or directed any of the research reported in this article. The remaining authors declare no competing interests. (© 2021 The Authors.)
Databáze:	MEDLINE
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