Abstract
BackgroundGastric 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.MethodsIn 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.ResultsOur 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.ConclusionsOur study indicates that B7H3 is an attractive target for GC therapy, and B7H3 has high potential for clinical application.
Highlights
Gastric cancer (GC) has a poor prognosis and limited therapeutic options
B7H3 is highly expressed on GC To analyze the expression of B7H3 in GC, mRNA extracted from tumor and peritumor tissues was used for RT-PCR assay
Results of RT-PCR assay are shown that B7H3 is highly expressed on GC, expression of B7H3 is significantly associated with the clinical stage of GC patients (Fig. 1A and B)
Summary
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. With deepened understanding of the molecular biological characteristics of gastric cancer, new gastric cancer treatment strategies were examined, and monoclonal antibody-targeted drug therapy and immunotherapy brought hope to patients with gastric cancer [4]. As a therapeutic strategy for malignant diseases, chimeric antigen receptor (CAR) T cells have therapeutic potential in antitumor treatment [6]. More than five CAR-T cell products have been used clinically in the treatment of hematologic malignancies but not yet for solid tumors [8]. The function of CAR-T cells is restricted to antigen specificity [9]. It is imperative to seek for new potent antigen
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