Abstract 5067: Identify the combination efficacy and immune regulation of Abraxane combines with human IL-15 albumin binding domain fusion protein on pancreatic ductal adenocarcinoma animal model

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the hardest medical challenge in the world. Nab-paclitaxel is significantly more effective chemotherapy drugs than paclitaxel formulated as Cremophor EL. In this study, we reported the immune effect of Abraxane to combine with our new design recombinant human IL-15 fused with albumin binding domain (hIL-15-ABD) on subcutaneously Panc02 and orthotopically KPC PDAC animal models. In our results, the combination treatment greatly reduced the subcutaneous tumor growth in Panc02 and KPC bearing models, compared with vehicle group. Furthermore, the combinational therapy successfully buildup the anticancer immunity microenvironment (TME) through increasing the activation of effector cells, such as of NK cells (CD3-/CD49b+/NK1.1+) and CD8+ T (CD8+/IFN-γ+/IL-2+) cells. Moreover, combination therapy may also decrease the accumulation of immunosuppressvie cells such as MDSCs (CD11b+/Gr-1+) and Tregs (CD4+/CD25+/Foxp3+). The combination of Abraxane and hIL-15-ABD were also reduced the NF-κB-mediated immunosuppressive markers, including IDO, Foxp3 and VEGF. In conclusion, Abraxane combined with hIL-15-ABD enhanced immue effector cells involved in both innate and adaptive immunities, reduced the TME’s immunosuppressive cells, and displayed superior inhibitory effect on both subcutaneous and orthotopic syngeneic murine pancreatic ductal adenocarcinoma models than that of either monotherapy. These results suggest that combinational therapy of Abraxane and hIL-15-ABD could be a promising treatment stratedgy for PDAC. Citation Format: Po-Fu Yueh, Fei-Ting Hsu, Keng-Li Lan. Identify the combination efficacy and immune regulation of Abraxane combines with human IL-15 albumin binding domain fusion protein on pancreatic ductal adenocarcinoma animal model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5067.