Abstract 4401: Tumor-associated antigen gene-loading polyplex micelle is a promising platform for anti-cancer DNA vaccine

Abstract

Abstract Backgrounds: Polyplex micelle attracts an increasing attention as a gene carrier, because of efficient gene transduction and biocompatibility in vivo. In this study, we examined the potential of polyplex micelle carrying genes encoding tumor-associated antigen (TAA): squamous cell carcinoma antigen recognized by T cells-3, CD40L and GM-CSF as a DNA vaccine platform in mouse tumor models with different types of major histocompatibility antigen complex (MHC). Methods and Results: Intraperitoneal administration of polyplex micelles were predominantly distributed and expressed in the lymph nodes, spleen and liver. The triple DNA vaccine significantly prolonged the survival of mice harboring peritoneal dissemination of CT26 colorectal cancer compared with mock controls, of which long-survivor mice induced complete rejection of re-challenged CT26 tumors. The DNA vaccine also inhibited the growth and metastasis of subcutaneous CT26 and Lewis lung cancers in BALB/c and C57BL/6 mice, respectively, which represent different MHC haplotypes. The DNA vaccine highly stimulated both cytotoxic T lymphocyte and natural killer cell activities, and increased the infiltration of CD11c+-DC, CD4+ and CD8a+ T cells into tumors. Depletion of CD4+ or CD8a+ cells using their neutralizing antibodies deteriorated the anti-tumor efficacy of the DNA vaccine. Conclusions: TAA/CD40L+GM-CSF gene-loaded polyplex micelle is a novel vaccine platform to elicit tumor rejection immunity regardless of recipient's MHC-haplotype. Note: This abstract was not presented at the meeting. Citation Format: Lin Cui, Kouichi Furugaki, Kensuke Osada, Kazunori Kataoka, Kenji Nakano. Tumor-associated antigen gene-loading polyplex micelle is a promising platform for anti-cancer DNA vaccine. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4401. doi:10.1158/1538-7445.AM2015-4401