Abstract
Introduction:
As an immune checkpoint molecule that is overexpressed in cervical and breast cancer, CD155 represents an attractive target for chimeric antigen receptor (CAR) T-cell therapy. However, it is crucial to thoroughly assess the efficacy and safety of CD155-based CAR T cells in preclinical models before considering clinical translation.
Methods:
In this study, we developed a CD155-based CAR comprising the extracellular domain of the human TIGIT, 4-1BB, and CD3z signaling domains and utilized a murine model of cervical and breast cancer to comprehensively evaluate the antitumor responses elicited by the CD155-based CAR T cells. The CAR construct was specifically designed to recognize and target CD155-expressing tumor cells.
Results:
The results of our study indicated that CD155 exhibits positive staining in the majority of clinical cervical and breast cancer tissues while showing no or low staining in normal tissues. In addition, we observed a correlation between the expression level of CD155 and the proliferation of malignant tumor cells. CD155-based CAR T cells effectively recognize and eliminate CD155-expressing tumor cells in vitro. Moreover, in vivo experiments using a murine model of cervical and breast cancer revealed that the administration of these CAR T cells leads to significant regression of established tumors without causing any observable toxicity. In addition, the clearance of CD155-positive tumor cells can effectively eliminate tumor cells that exhibit high proliferation rates. This suggests that the treatment approach may offer a safe and effective option for patients with cervical and breast cancer.
Discussion:
Overall, our findings provide strong evidence for the efficacy and safety of CD155-based CAR T-cell therapy in cervical and breast cancer. This study contributes to the growing body of research supporting the potential clinical application of CD155-targeted immunotherapy for patients with cervical and breast cancer.