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Development of Hematopoietic Stem Cell-Engineered Invariant Natural Killer T Cell Therapy for Cancer.

Abstract：

:Invariant natural killer T (iNKT) cells are potent immune cells for targeting cancer; however, their clinical application has been hindered by their low numbers in cancer patients. Here, we developed a proof-of-concept for hematopoietic stem cell-engineered iNKT (HSC-iNKT) cell therapy with the potential to provide therapeutic levels of iNKT cells for a patient's lifetime. Using a human HSC engrafted mouse model and a human iNKT TCR gene engineering approach, we demonstrated the efficient and long-term generation of HSC-iNKT cells in vivo. These HSC-iNKT cells closely resembled endogenous human iNKT cells, could deploy multiple mechanisms to attack tumor cells, and effectively suppressed tumor growth in vivo in multiple human tumor xenograft mouse models. Preclinical safety studies showed no toxicity or tumorigenicity of the HSC-iNKT cell therapy. Collectively, these results demonstrated the feasibility, safety, and cancer therapy potential of the proposed HSC-iNKT cell therapy and laid a foundation for future clinical development.

journal_name

Cell Stem Cell

journal_title

Cell stem cell

authors

Zhu Y,Smith DJ,Zhou Y,Li YR,Yu J,Lee D,Wang YC,Di Biase S,Wang X,Hardoy C,Ku J,Tsao T,Lin LJ,Pham AT,Moon H,McLaughlin J,Cheng D,Hollis RP,Campo-Fernandez B,Urbinati F,Wei L,Pang L,Rezek V,Berent-Maoz B,Ma

doi

10.1016/j.stem.2019.08.004

subject

Has Abstract

pub_date

2019-10-03 00:00:00

pages

542-557.e9

issue

4

eissn

1934-5909

issn

1875-9777

pii

S1934-5909(19)30339-X

journal_volume

25

pub_type

杂志文章

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