Drug Discovery Seminar - Xuefei Huang, PhD
Development of next generation glycoconjugate based anticancer vaccines
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 using mucin-1 (MUC1) as a representative antigen. Mucin-1 (MUC1) is one of the top ranked tumor associated antigens. Multiple mutants of Qβ have been designed to reduce anti-carrier antibody responses. In order to generate high anti-MUC1 immunity as potential anti-cancer vaccines, MUC1 peptides and glycopeptides have been covalently conjugated to Qβ and mutants. Immunization of mice with these constructs led to super strong antibody responses with IgG titers over one million, which are one of the highest IgG titers reported to date. Furthermore, the high IgG antibody levels persisted for more than six months. Besides remarkably high titers of antibodies, the constructs also elicited MUC1 specific cytotoxic T cells, which can selectively kill MUC1 positive tumor cells. The unique abilities of MUC1-Qβ conjugates to induce both antibody and cytotoxic T cell immunity targeting tumor cells bode well for future translation of the constructs as anti- tumor vaccines.
Date: Friday, December 3
Time: 09:00 AM
Location: IQ Lobby & Zoom
Host: Dr. Rick Neubig (firstname.lastname@example.org)