Year: 2021
Type: article
Abstract: 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.
Source: Cell Reports Medicine
Authors: Yan-Ruide Li, Yang Zhou, Yu Jeong Kim, Yanni Zhu, Feiyang Ma, Jiaji Yu, Yu-Chen Wang, Xianhui Chen, Zhe Li, Samuel Zeng, Xi Wang, Derek Lee, Josh Ku, Tasha Tsao, Christian Hardoy, Jie Huang, Donghui Cheng, Amélie Montel-Hagen, Christopher S. Seet, Gay M. Crooks, Sarah M. Larson, Joshua P. Sasine, Xiaoyan Wang, Matteo Pellegrini, Antoni Ribas, Donald B. Kohn, Owen Witte, Pin Wang, Lili Yang
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,200
Funders: California Institute for Regenerative Medicine, Concern Foundation, Stop Cancer, University of Southern California, National Institutes of Health, University of California, Los Angeles, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles
Awards: G3103422320, Decoupling Bidirectional EphB/ephrinB2 in Multiple Myeloma, G4554880003, UCLA-Caltech Medical Scientist Training Program, G5670214711, G589664268, Stem Cell-Engineered Invariant Natural Killer T Cells for Cancer Therapy, Stem Cell-Based iNKT Cell Therapy for Cancer, Preclinical Development of An HSC-Engineered Off-The-Shelf iNKT Cell Therapy for Cancer, G9000269057, G9000342382, UCLA SPORE in Brain Cancer, Multidisciplinary Training in Microbial Pathogenesis, UCLA Tumor Immunology Institutional Training Grant, Cancer Center Support Grant
OpenAlex ID: W3211538813