Effective and persistent antitumor activity of HER2-directed CAR-T cells against gastric cancer cells in vitro and xenotransplanted tumors in vivo
Protein & Cell
;
(12): 867-878, 2018.
Article
in English
| WPRIM
| ID: wpr-757003
ABSTRACT
Human epidermal growth factor receptor 2 (HER2) proteins are overexpressed in a high proportion of gastric cancer (GC) cases and affect the maintenance of cancer stem cell (CSC) subpopulations, which are used as targets for the clinical treatment of patients with HER2-positive GC. Despite improvements in survival, numerous HER2-positive patients fail treatment with trastuzumab, highlighting the need for more effective therapies. In this study, we generated a novel type of genetically modified human T cells, expressing a chimeric antigen receptor (CAR), and targeting the GC cell antigen HER2, which harbors the CD137 and CD3ζ moieties. Our findings show that the expanded CAR-T cells, expressing an increased central memory phenotype, were activated by the specific recognition of HER2 antigens in an MHC-independent manner, and effectively killed patient-derived HER2-positive GC cells. In HER2-positive xenograft tumors, CAR-T cells exhibited considerably enhanced tumor inhibition ability, long-term survival, and homing to targets, compared with those of non-transduced T cells. The sphere-forming ability and in vivo tumorigenicity of patient-derived gastric cancer stem-like cells, expressing HER2 and the CD44 protein, were also inhibited. Our results support the future development and clinical application of this adoptive immunotherapy in patients with HER2-positive advanced GC.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pathology
/
Stomach Neoplasms
/
Therapeutics
/
Tumor Cells, Cultured
/
Receptors, Antigen, T-Cell
/
Receptor, ErbB-2
/
Allergy and Immunology
/
Mice, Inbred BALB C
/
Mice, Nude
/
Neoplasms, Experimental
Limits:
Animals
/
Humans
Language:
English
Journal:
Protein & Cell
Year:
2018
Type:
Article
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