Generation of tumor-targeted human T lymphocytes from induced pluripotent stem cells for cancer therapy.
Progress in adoptive T-cell therapy for cancer and infectious diseases is hampered by the lack of readily available, antigen-specific, human T lymphocytes. Pluripotent stem cells could provide an unlimited source of T lymphocytes, but the therapeutic potential of human pluripotent stem cell-derived lymphoid cells generated to date remains uncertain. Here we combine induced pluripotent stem cell (iPSC) and chimeric antigen receptor (CAR) technologies to generate human T cells targeted to CD19, an antigen expressed by malignant B cells, in tissue culture. These iPSC-derived, CAR-expressing T cells display a phenotype resembling that of innate γδ T cells. Similar to CAR-transduced, peripheral blood γδ T cells, the iPSC-derived T cells potently inhibit tumor growth in a xenograft model. This approach of generating therapeutic human T cells 'in the dish' may be useful for cancer immunotherapy and other medical applications.
Center for Cell Engineering, Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Maria
M
Themeli
Christopher C
CC
Kloss
Giovanni
G
Ciriello
Victor D
VD
Fedorov
Fabiana
F
Perna
Mithat
M
Gonen
Michel
M
Sadelain
D000818:Animals; D018941:Antigens, CD19 / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002860:Chromium Radioisotopes; D016000:Cluster Analysis; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D008297:Male; D051379:Mice; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D010641:Phenotype; D015202:Protein Engineering; D011946:Receptors, Antigen; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology
D018941:Antigens, CD19; D002860:Chromium Radioisotopes; D011946:Receptors, Antigen