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Antitumor responses in gastric cancer by targeting B7H3 via chimeric antigen receptor T cells
Fengqiang Sun1, Xiaomei Yu2, Ruixue Ju1
1Department of Clinical Laboratory, Weifang People's Hospital, Weifang, 261000, Shandong, China.
Background:
Gastric cancer (GC) has a poor prognosis and limited therapeutic options. As a new promising cancer therapeutic approach, chimeric antigen receptor (CAR)-T cells represent a potential GC treatment. We investigated the antitumor activity of CAR-T cells target-B7H3 in GC.
Methods:
In our study, expression of B7H3 was examined in GC tissues and explored the tumoricidal potential of B7H3-targeting CAR-T cells in GC. B7H3-directed CAR-T cells with a humanized antigen-recognizing domain was generated. The anti-tumor effects of this CAR-T cell were finally investigated in vitro and in vivo.
Results:
Our results show that B7H3-directed CAR-T cells efficiently killed GC tumor cells. In addition, we found that B7H3 is correlated with tumor cell stemness, and anti-B7H3 CAR-T can simultaneously target stem cell-like GC cells to improve the treatment outcome.
Conclusions:
Our study indicates that B7H3 is an attractive target for GC therapy, and B7H3 has high potential for clinical application.
Insights
Chimeric antigen receptor (CAR)-T cells targeting B7H3 show promise for treating gastric cancer (GC). These B7H3-targeting CAR-T cells effectively kill GC cells and may improve outcomes by targeting cancer stem cells.
Area of Science:
- Immunotherapy
- Oncology
- Cellular Therapy
Background:
- Gastric cancer (GC) presents significant challenges with poor prognosis and limited treatment options.
- Chimeric antigen receptor (CAR)-T cell therapy is an emerging approach for cancer treatment.
- The potential of CAR-T cells targeting B7H3 in GC requires further investigation.
Purpose of the Study:
- To investigate the antitumor activity of B7H3-targeting CAR-T cells in gastric cancer.
- To evaluate B7H3 expression in GC tissues.
- To explore the correlation between B7H3 and GC stemness.
Main Methods:
- Examined B7H3 expression in GC tissues.
- Generated humanized B7H3-directed CAR-T cells.
- Assessed anti-tumor effects of CAR-T cells in vitro and in vivo.
Main Results:
- B7H3-directed CAR-T cells demonstrated efficient killing of GC tumor cells.
- B7H3 expression was found to correlate with tumor cell stemness.
- Simultaneous targeting of stem cell-like GC cells by anti-B7H3 CAR-T cells improved treatment outcomes.
Conclusions:
- B7H3 is identified as a promising therapeutic target for gastric cancer.
- B7H3-targeting CAR-T cells exhibit significant potential for clinical application in GC treatment.
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