Abstract LB-086: CD3 MOSPD2 bi specific antibody significantly prolongs survival in a model of metastatic human cervical cancer without any evidence of toxicity

Abstract

Abstract Introduction: We have previously showed that motile sperm domain-containing protein 2 (MOSPD2), is highly expressed in multiple solid tumors and cancer cell lines but has low/undetectable levels in healthy tissues, implying that MOSPD2 can be an effective target for directed killing of tumor cells. We developed CD3xMOSPD2 bi-specific IgG antibodies (BsAb) that induced T-cell activation and yielded profound death of target tumor cells in-vitro. Experimental procedure: NSG mice were injected subcutaneously with the metastatic cervical cancer HeLa cell line (day 0). Freshly isolated human PBMC were transferred I.P when tumors volume reached an average of 150mm3 (day 29). Subsequently, mice were treated I.V with control IgG antibody or CD3xMOSPD2 BsAb and monitored for survival. To assess in-vivo T-cell activation, serum collected 6hr after first antibody treatment was analyzed for cytokines level. Results: Treatment with CD3xMOSPD2 BsAb, significantly increased serum concentration of IFN-γ, IL-6 and TNF-α compared with control IgG-treatment. Strikingly, by day 65, survival rate of CD3xMOSPD2 BsAb treated mice was 90% compared with only 10% in the control IgG-treated group (n=9-10; p=0.00106). No evidence of toxicity or off target activity was detected. Conclusions: Our data show that CD3xMOSPD2 bi-specific antibody induces T-cell activation in-vivo and significantly extends the survival of mice carrying established metastatic cervical cancer. These results highlight the potential of bi-specific mediated immuno-oncology therapy for the treatment of MOSPD2-positive metastatic solid tumors. Citation Format: Niva Yacov, Oshrat Propheta-Meiran, Pinhas Kafri, Yaniv Salem, Itzhak Mendel, EYAL BREITBART. CD3 MOSPD2 bi specific antibody significantly prolongs survival in a model of metastatic human cervical cancer without any evidence of toxicity [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 LB-086.