CD155-based Chimeric Antigen Receptor T cells: A Promising Immunotherapy for Cervical and Breast Cancers

Jun Ma^1,2,3*Wenjing Zhu^1,3Rui Zhao^1,3Qianqian Shi^1,2,3Yang Fang^1,2,3Yangnan Ding^1,2,3Enwu Yuan^1,2,3Kai Zhang^1,2,3*Xin Zhao^2,4*

• ¹Department of Laboratory Medicine, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
• ²Tianjian Laboratory of Advanced Biomedical Sciences, School of Life Sciences, Zhengzhou University, Zhengzhou, Henan Province, China
• ³Zhengzhou Key Laboratory for In Vitro Diagnosis of Hypertensive Disorders of Pregnancy, zhenhzhou, China
• ⁴The Radiology Department, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, ZHENGZHOU, China

As an immune checkpoint molecule that is overexpressed in cervical and breast cancers, CD155 represents an attractive target for 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. In this study, we developed a CD155-based CAR comprising the extracellular domain of human TIGIT, 4-1BB, and CD3z signaling domains, and utilized a murine model of cervical and breast cancers to comprehensively evaluate the antitumor responses elicited by CD155-based CAR-T cells. The CAR construct was specifically designed to recognize and target CD155-expressing tumor cells. The results of our study indicated that CD155 exhibited positive staining in the majority of clinical cervical and breast cancers, while showing no or low staining in normal tissues. Additionally, we observed a correlation between the expression levels 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 cancers revealed that 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 suggested that the treatment approach may offer a safe and effective option for patients with cervical and breast cancers. Overall, our findings provide strong evidence for the efficacy and safety of CD155-based CAR-T cell therapy in cervical and breast cancers. 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.