Development of allogeneic HSC-engineered iNKT cells for off-the-shelf cancer immunotherapy.
Cell Rep Med
; 2(11): 100449, 2021 11 16.
Article
in En
| MEDLINE
| ID: mdl-34841295
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 (AlloHSC-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 AlloHSC-iNKT cell products and lay a foundation for their translational and clinical development.
Key words
CAR-engineered conventional αß T cells; HLA-ablated universal HSC-iNKT cells; allogeneic HSC-engineered iNKT cells; allogeneic off-the-shelf cell therapy; allorejection; cancer immunotherapy; chimeric antigen receptor; graft-versus-host disease; hematopoietic stem cell; invariant natural killer T cells
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Hematopoietic Stem Cells
/
Natural Killer T-Cells
/
Cell Engineering
/
Allogeneic Cells
/
Immunotherapy
/
Neoplasms
Limits:
Animals
/
Humans
Language:
En
Journal:
Cell Rep Med
Year:
2021
Document type:
Article
Affiliation country:
United States