565 Combinatorial HSCs and anti-PD-1 therapy in microsatellite stable colorectal cancer

Background Colon cancer (CRC) is the second leading cause of cancer-related deaths in US. CRC incidence on rise and there an alarming increase young onset cases. Immune checkpoint inhibitors (ICIs) have yielded promising anti-tumor results microsatellite instable high (MSI-high) patients, which represent only 15% tumors. The remaining 85% are denoted as stable (MSS) unresponsive to ICI. Using a murine glioma model, our group has previously found combination anti-PD-1 transfer hematopoietic stem cells (HSCs) can sensitize mice that resistant alone. We evaluated survival after treatment with this combinatorial platform 3 or 5 days post-implantation subcutaneous CRC-bearing also phenotyped splenic compartment at endpoint. Methods 1x106 MSS cells, CT26, were subcutaneously injected into right flank BALB/cJ mice. later, HSCs isolated from naïve through tail vein CT26-bearing given 10 mg/kg anti-PD-1. Mice additional doses for total either every days. sacrificed when tumors reached 1.5 cm its widest point spleens excised stained flow cytometry. Results When treated HSC/anti-PD-1 post-tumor implantation, we observed statistically significant received relative no control (p=0.0034, Mantel-Cox long-rank test) well alone (p=0.0462, log-rank test. In same day cohort, differences frequency T cell populations observed. However, therapy had CD11c+ MHC II+ dendritic (DCs) (p=0.0364, Mann-Whitney t test). compared (p=0.0024, HSC monotherapy Conclusions These suggest represents therapeutic axis model CRC. addition, DCs suggests mechanism behind response may be expansion within periphery. Ethics Approval All animal work approved University Florida IACUC # 201910777