Abstract 2003: Evaluation of liposome encapsulated sunitinib efficacy and immune modulation on renal cell carcinoma

Abstract

Abstract Renal cell carcinoma (RCC) is one of the deadliest malignant tumors worldwide. The RCC’s standard treatments are including surgery, radiation, and chemotherapy. SUTENT® (sunitinib) was approved by US Food and Drug Administration (FDA) in 2016 to treat advanced RCC. According to the results from the clinical trial, sunitinib is associated with a higher objective response rate and survival rate than IFN-α, which indicates that it is an effective multiple tyrosine kinase inhibitor (TKi) against advanced RCC. Meanwhile, recent studies demonstrated sunitinib could cause tumor immune surveillance by upregulated autophagy to inhibit tumor PD-L1 expression. However, sunitinib targets not only tumor tissue but also multiple organs in the human body, which causes many serious side effects and even leads to death. In order to reduce the toxicity of sunitinib, our group design a novel nanocarrier by PEGylated liposome to encapsulate sunitinib (lipo-sunitinib). The PEGylated liposome could passively target tumor tissue by extravasation of nanoparticles through increased permeability of the tumor vasculature (enhanced permeability and retention, EPR effect). Moreover, the PEGylation on the liposome surface could prolong liposome half-life in the body through increased particle size. Through the EPR effect and PEGylation of lipo-sunitinib to target tumor cells precisely, we successfully increased RCC orthotopic tumor inhibition in mouse models compared with vehicle and sunitinib groups. Furthermore, the RCC tumor immunofluorescence staining revealed lipo-sunitinib had higher activated effector T cells (CD8+IL-2+IFN-γ+) and type 1 dendritic cells (CD11c+CD24+MHCII+) infiltration and lower vessel formation than sunitinib group. The flow cytometry also demonstrated that lipo-sunitinib had increased anti-tumor immune cells and inhibited immune suppressors in the systemic system. More importantly, lipo-sunitinib showed lower toxicity in mouse livers, hearts, and kidneys compared to the sunitinib group. Our results suggested lipo-sunitinib could inhibit tumor growth and prolong survival rate by modulating a positive anti-tumor microenvironment and anti-angiogenesis effects. In sum, with the polish of the delivery system, our novel nanodrug lipo-sunitinib could be a potential new treatment strategy for RCC patients. Citation Format: Po-Fu Yueh, Yuan Chang, Keng-Li Lan, Fei-Ting Hsu. Evaluation of liposome encapsulated sunitinib efficacy and immune modulation on renal cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2003.