Abstract 858: Development of next generation carbohydrate-based vaccines

Abstract The development of an effective vaccine construct against tumor associated carbohydrate antigens (TACAs) is an attractive approach towards cancer treatment and prevention. However, a significant challenge is that TACAs are only weakly immunogenic and direct administration of TACAs cannot elicit a powerful antibody response to protect the host from cancer development. In this presentation, we will present our strategies in engineering virus like particle bacteriophage Qβ to significantly enhance the immunogenicity of TACAs as potential anti-cancer vaccines. With its abilities to display antigens in a highly organized manner, Qβ can be a powerful carrier to deliver the antigen to the immune system and activate adaptive immunity. We have engineered Qβ to reduce the antibody responses against the carrier and incorporate T cell epitopes to induce a comprehensive immune response activating both humoral and cellular immunity. With the new Qβ carrier in hand, ganglioside GD2 has been explored as a representative antigen. Ganglioside GD2 is an appealing TACA due to its overexpression on many types of tumor cells. However, its low immunogenicity and the significant side effects observed with anti-GD2 antibodies present significant obstacles for vaccines. To overcome these, a new GD2 derivative bearing an N-acetamide (NHAc) at its non-reducing end neuraminic acid (9NHAc-GD2) has been designed to mimic the 9-O-acetylated-GD2 (9OAc-GD2), a GD2 based antigen with a restricted expression on tumor cells. 9NHAc-GD2 was synthesized efficiently via a chemoenzymatic method and subsequently conjugated with a powerful carrier bacteriophage Qβ. Mouse immunization with the Qβ-9NHAc-GD2 conjugate elicited strong and long-lasting IgG antibodies, which were highly selective toward 9NHAc-GD2 with little cross-recognition of GD2. Immunization of canines with Qβ-9NHAc-GD2 showed the construct was immunogenic in canines with little adverse effects, paving the way for future clinical translation to humans. Building on these results, we are further engineering the 9NHAc-GD2 antigen to improve its immunogenicity. Our latest efforts in designing new GD2 antigens and evaluating them in tumor models will be discussed. Citation Format: Xuefei Huang. Development of next generation carbohydrate-based vaccines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 858.