Bispecific antibody targeting CD155 mediates T-cell immunotherapy against human gynecological malignancies.

T cells are crucial regulators in cancer treatment due to their cytotoxic ability. Recently, immunotherapies based on bispecific antibodies (Bi-Ab) have achieved remarkable effects in cancer treatment, attributed to their capability of recruiting and activating T cells to kill tumors. In the present study, we investigated whether CD155 is an effective target for T-cell-mediated immunotherapy against human gynecological malignancies. We demonstrated that CD155 is expressed on common gynecological tumor cells, including cervical, uterine, and ovarian cancers. Next, we evaluated the specific cytotoxic activity of T cells armed with CD155Bi-Ab (CD155Bi-T cells) against tumor cells. Compared with control T cells treated with separate anti-CD155 and anti-CD3 mAbs, CD155Bi-T cells exhibited significant cytotoxicity against CD155-positive gynecological tumor cells. Specifically, in the luciferase assay, the cytotoxicity of CD155Bi-T cells was 2.67-fold higher than that of control T cells at an effector/target ratio of 5:1, indicating a significant enhancement in tumor-killing activity. This enhanced cytotoxic activity was further supported by increased expression of activation markers (CD69 and 4 - 1BB), higher production of T-cell-derived cytokines (IL- 2, IFN-γ, and TNF-α), and elevated levels of the cell-killing mediators (perforin and granzyme B). Taken together, our findings demonstrate that CD155 is a promising target for gynecological tumors, and CD155Bi-T cells hold significant potential for immunotherapy against CD155⁺ gynecological malignancies.