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Chemistry Colloquium - Xuefei Huang

"Fighting cancer with a sweet bullet: the development of carbohydrate based anticancer vaccines"

Presented by Xuefei Huang, Michigan State University

Hosted by Koji Nakanishi

Thursday, November 7, 2013

1:30 - Meet the Speaker, Room 328 Havemeyer
4:00 - Tea & Cookies, Room 328 Havemeyer
4:30 - Seminar, Room 209 Havemeyer

There are many antigenic carbohydrate structures on cancer cell surfaces.  The development of an effective vaccine construct against these tumor associated carbohydrate antigens (TACAs) is an attractive approach towards cancer treatment.  However, a serious challenge is that the TACAs are only weakly immunogenic and direct administration of TACAs cannot elicit a powerful immune response to protect the host from cancer development.  In this talk, we will present our results on the development of virus-like particles such as bacteriophage Qbeta (Qβ) as a novel platform to significantly enhance the immunogenicity of TACAs.

The Tn glycan, which is overexpressed on numerous cancer cell surfaces, was selected as the antigen for our study.  Previously it has been shown to be difficult to induce a strong T cell-dependent immune response against the monomeric form of Tn.  We first synthesized Tn antigens that were conjugated regioselectively to Qb.  The Qb-glycoconjugates were then injected into mice and pre- and post-immune antibody levels in the mice sera were established.  High total antibody titers and, more importantly, high IgG titers specific for Tn were obtained in the post-immunization, suggesting the induction of T cell-dependent antibody isotype switching by the glycoconjugate.  The antibodies generated were able to recognize Tn antigens presented in their native conformations on the surfaces of cancer cells.  Importantly, we discovered that the local density rather than the total amount of the Tn antigen was critical for high antibody responses once the amount of Tn passed a threshold level.  Moreover, the vaccine construct provided significant protection against the development of an aggressive tumor model in mice.  These results suggest that virus-like particle Qβ can greatly enhance the immunogenicity of weak antigens such as Tn and this provides a promising tool for the development of carbohydrate based anti-cancer vaccines.

Xuefei Huang received his undergraduate education from the University of Science and Technology of China. In 1994, he came to the US and joined the group of Prof. Koji Nakanishi at Columbia University, where he worked on the development of circular dichroism methods for absolute configurational assignments and bio-organic studies of neurotoxins.  Upon receiving his Ph.D. degree in 1999, he joined Prof. Chi-Huey Wong's group at the Scripps Research Institute as a postdoctoral researcher, where he was exposed to the wonderful world of glyco-chemistry and glycobiology.  After another postdoc stint back to Columbia University with Prof. Nakanishi, he started his independent research career at the University of Toledo in 2002. He was promoted to associate professor in 2006 with tenure.  In 2008, he moved to Michigan State University and was promoted to full professor in 2012.  His research interests are in several areas including the development of glyco-nanoparticles for biological applications, total synthesis of complex oligosaccharides and glycoconjugates, and the development of carbohydrate based anti-cancer vaccines.