Abstract LB-132: MOSPD2: A novel target for Bi-specific Ab mediated killing of tumor cells

Abstract

Abstract Introduction: We have previously described motile sperm domain-containing protein 2 (MOSPD2) as essential for breast cancer metastasis in vitro and in vivo. In this study, we detected high expression of MOSPD2 in different organ tumors and cancer cells, and subsequently developed CD3xMOSPD2 BiTE, a firstly generated bi-specific antibody that directs killing of MOSPD2 expressing cancer cells. Experimental procedure: The prevalence of MOSPD2 was evaluated by IHC in tissue microarrays layered with cores, representing multiple organ tumors and normal tissue. MOSPD2 abundance was scored according to the staining intensity on a scale from 0 to 3. Human monoclonal antibody against the extracellular region of human MOSPD2 was generated. To determine the presence of cell surface MOSPD2 expression, FACS analysis was performed on cell lines derived from different tumor origins. BiTE was generated to comprise the scFv region of anti-human CD3 and the scFv region of a human anti-human MOSPD2. Cancer cell lines were co-cultured with freshly isolated T-cells or effector CD8 T-cells in the presence of CD3xMOSPD2 or a control BiTE. Cancer cell survival rate and T cell activation was determined after 2-3 days by FACS. Results: MOSPD2 expression was evident in the majority of organ tumors, with high prevalence in tumors such as colon, liver and breast. Normal tissue was either devoid of MOSPD2, or had low expression relative to its parallel tumor tissue. Within normal or normal adjacent tissue (NAT), staining could be detected primarily in lymphoid tissues where myeloid cells abundantly reside. FACS staining using a human anti-MOSPD2 mAb demonstrated that MOSPD2 is expressed on the surface of different cancer cell lines. Employing CD3xMOSPD2 BiTE on myeloid or solid tumor-derived cell lines induced T-cell activation and yielded profound killing of cancer cells. Conclusions: IHC staining demonstrates MOSPD2 expression profile supportive of targeting cancer cells. CD3xMOSPD2 BiTE directs T-cells to MOSPD2 expressing cancer cells and induces their destruction in-vitro. Therefore, we propose CD3xMOSPD2 bi-specific antibodies as a potential therapy for the treatment of cancer via a unique target, directed for the destruction of hematological cancers and solid tumors expressing MOSPD2. Citation Format: Itzhak Mendel, Yaniv Salem, Niva Yacov, Osharat Prhopheta-Meiran, Pinhas Kafri, Eyal Breitbart. MOSPD2: A novel target for Bi-specific Ab mediated killing of tumor cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-132.