Developing bacteriophage Qβ as versatile carrier for anti-carbohydrate cancer vaccine: influence of antigen design on antibody responses (VAC8P.998)

Abstract Vaccines that aim to stimulate the immune system to eradicate tumor cells are very attractive method for cancer therapy. One such strategy, active vaccination against tumor associated carbohydrate antigens (TACAs), which are overexpressed on malignant cells and strongly correlated with tumor progression and metastasis, has shown high potential in clinical studies. However, two major challenges need be circumvented to develop effective TACA anticancer vaccines. First, TACAs are self-antigens and tolerated by the immune system; Second, TACAs are weak T cell independent antigens and cannot generate long lasting immune responses when administered alone. We are interested in exploration of bacteriophage Qβ as versatile platforms for the development of carbohydrate based cancer vaccine. The highly repetitive array of subunit in Qβ permits the organized display of antigens on the surface of the particle. The Qβ also contains natural T-helper epitopes and pathogen associated molecular patterns, which can engage innate immunity and activate the immune system. Herein, we present the vaccination studies with Tn antigen conjugated to bacteriophage Qβ. The effect of antigen density, nature of linker, and immunization routes on the quality and diversity of antibody responses was analyzed. With the optimal construct, significant preventive and therapeutic effects were achieved on highly aggressive TA3Ha tumor model.