Abstract 5592: MOSPD2 a novel target for bi-specific antibody mediated solid tumor cells immune death

Abstract

Abstract Introduction: We have previously identified motile sperm domain-containing protein 2 (MOSPD2) as key regulator of monocyte motility. While MOSPD2 is normally expressed by myeloid cells with low/undetectable levels in healthy tissues, high expression of MOSPD2 is detected in multiple solid tumors and cancer cell lines. MOSPD2 expression was highly elevated in invasive and metastatic breast cancer but not in in-situ tumors, and our data indicate that it is essential for breast cancer cell metastasis in vitro and in-vivo. Based on its abundant-and specific solid tumor expression profile, MOSPD2 may serve as a target for immune-mediated targeting of tumor cells. Experimental procedure: We have developed CD3xMOSPD2 bi-specific IgG antibodies (BsAb) for killing of MOSPD2+ cancer cells. Binding of the BsAbs to cancer cells and T-cells was validated by flow cytometry. For efficacy, cancer cell lines were co-cultured with effector CD8 T-cells in the presence of CD3xMOSPD2 BsAb or a control IgG. Cancer cell survival and T-cell activation was determined by flow-cytometry and ELISA for IFN-gamma. Results: Flow-cytometry confirmed surface binding of BsAbs to cancer cell lines and CD8 T-cells. Employing CD3xMOSPD2 IgG BsAb on cancer cell lines induced T-cell activation and yielded profound death of target tumor cells. Conclusions: CD3xMOSPD2 bi-specific antibodies potentially offer a new immuno-oncology therapeutic tool for treatment of various MOSPD2-positive solid tumors. Citation Format: Yaniv Salem, Niva Yacov, Oshrat Propheta-Meiran, Pinhas Kafri, Itzhak Mendel, Eyal Breitbart. MOSPD2 a novel target for bi-specific antibody mediated solid tumor cells immune death [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5592.