1230PTargeting myeloid-derived suppressor cells and T cells: Combination treatment with MTL-CEBPA and PD-1 antibody in a mouse syngeneic CT26 model

Abstract Background MTL-CEBPA is a myeloid modifier saRNA therapy which upregulates CEBPalpha and is the first saRNA therapy to enter clinical trials. We hypothesise that targeting myeloid-derived suppressor cells (MDSCs) with MTL-CEBPA and T cells with PD-1 antibody may enhance the therapeutic efficacy of each individual therapy. Methods CT26 syngeneic mice were randomised into 4 groups (n = 10) and treated with vehicle control, PD-1 antibody (10mg/kg, i.p., d1/d4 schedule, 7 doses), MTL-CEBPA (5mg/kg, i.v, d1/d3 schedule, 7 doses) or a combination of both compounds. RNA extracted from tumours at termination were analysed by Nanostring IO360 and myeloid innate immunity codeset. Results At 21 days of treatment, the average tumonur volumes in the MTL-CEBPA/PD-1 treated group were smallest and 3.0-fold smaller (p  Table . 1230P Individual genes that show synergistic effect. Calcilated as fold versus vehicle control. * p  PD-1 mAb MTL-CEBPA Combination Cd4 1.81 1.53 7.63 (*) Cd8a 1.29 1.22 3.68 (*) Cd8b1 1.51 (*) 1.02 4.62 (*) Cd3e 1.22 1.11 4.48 (*) Gzma 1.38 1.14 2.39 (*) Gzmb 1.76 1.51 (*) 3.86 Ifng 2.20 1.24 4.71 (**) Vegfa 1.18 1.04 0.94 Mki67 1.00 0.84 (**) 0.62 (**) Conclusions The study indicates enhanced anti-tumour activity when combining MTL-CEBPA with PD-1 antibody in the immunocompetent mouse CT26 colorectal cancer model. The combination treatment appears to result in increased penetration of TILs through modulation of immune activity in the tumour microenvironment. Legal entity responsible for the study MiNA Therapeutics. Funding MiNA Therapeutics. Disclosure M. Sodergren: Research grant / Funding (self): MiNA Therapeutics. C. Tan: Honoraria (self), Research grant / Funding (self): MiNA Therapeutics. V. Reebye: Honoraria (self), Leadership role, Research grant / Funding (self): MiNA Therapeutics. R. Habib: Honoraria (self), Leadership role: MiNA Therapeutics. D. Blakey: Honoraria (self), Leadership role: MiNA Therapeutics. N. Habib: Leadership role, Research grant / Funding (self): MiNA Therapeutics.