Redox-responsive linker improves the immunogenicity of Rhamnose-modified anti-cancer vaccine

• 1、School of Bioengineering, Jiangnan University,Wuxi,214122,China

Abstract：Tumor-associated carbohydrate antigens, such as sTn antigen, which are abundantly exposed on the surface of cancer cells, are one of the most important targets for the development of anti-cancer vaccines. Traditionally, the carbohydrate antigens are conjugated with carrier proteins to form glycoconjugate vaccines. However, the carrier proteins usually elicit too strong immune responses that suppress the immune responses against carbohydrate antigens. Our previous studies found that the carrier protein modified with Rhamnose (Rha) hapten could significantly enhance the immune responses against sTn. The Rha hapten can recruit endogenous anti-Rha antibodies and then target antigen-presenting cells to improve the antigen delivery. In the present study, we constructed a novel sTn-based anti-cancer vaccine by using a redox-responsive disulfide bond linker to carry the antibody-recruiting hapten Rha. The in vitro study and mouse study revealed that this redox-responsive linker can facilitate the lysosome escape and accelerate the release of antigen following with dramatically increased sTn-specific immune responses. The induced antibodies can successfully recognize the cancer cells with sTn expression and mediate complement-dependent cytotoxicity against cancer cells. This strategy of vaccine construct efficiently improves the efficacy of vaccine and could be further applied in vaccine industry.

Keywords： anti-cancer vaccine sTn antigen redox-responsive endogenous antibody lysosome escape