Geert-Jan Boons, PhD.

Utrecht University, Utrecht, Netherlands

Xuefei Huang, Ph.D.

Michigan State University, East Lansing, MI

Topic: Development of sialyl Lewis^a-based anti-cancer immunotherapy

Sialyl Lewis^a (sLe^a), also known as cancer antigen 19-9 (CA19-9), is a tumor associated carbohydrate antigen. The overexpression of sLe^a on the surface of a variety of cancer cells makes it an attractive target for anti-cancer immunotherapy. However, sLe^a based anti-cancer vaccines and monoclonal antibodies have been under-explored. In this presentation, the development of immunotherapy targeting sLe^a will be discussed.

To develop sLe^a based immunotherapy, sLe^a in a conjugable form is needed. Furthermore, to boost the antibody responses against sLe^a, it needs to be conjugated to an immunogenic carrier. We have developed an efficient stereoselective synthesis of sLe^a with an amine bearing linker by overcoming challenges related to low reactivities of sialic acid donor and stereochemical controls of sialylation.  The synthetic sLe^a was conjugated with a powerful carrier bacteriophage Qβ. Mouse immunization with the Qβ-sLe^a conjugate generated strong and long-lasting anti-sLe^a IgG antibody responses, which were superior to those induced by the corresponding conjugate of sLe^a with the benchmark carrier keyhole limpet hemocyanin. Antibodies elicited by Qβ-sLe^a were highly selective toward sLe^a structure, could bind strongly with sLe^a expressing cancer cells and human pancreatic cancer tissues, and kill tumor cells via complement mediated cytotoxicity. Furthermore, vaccination with Qβ-sLe^a or treatment with the anti-sLe^a monoclonal antibodies significantly protected the mice from tumor development in a metastatic cancer model. This is the first time that tumor protection was observed from a sLe^a based vaccine. These results highlight the significant potential of sLe^a as a promising cancer antigen for immunotherapy development.

Xinshan Ye, PhD

Peking University, Beijing, China

Topic: Donor preactivation-based glycan synthesis and potential therapeutic applications

Carbohydrates play important roles in life science, and the synthesis of structurally well-defined glycans faces great challenges. We have developed a glycosyl donor preactivation-based one-pot glycosylation strategy, and a series of complex glycans with biological importance have been synthesized by this protocol. Recently, based on the established platform for synthesizing glycans, we have realized the synthesis of some naturally-occurring glycans, leading to the identification of active compounds with therapeutic potentials. These include the synthesis and anti-pancreatic-cancer activity of polysaccharides from Panax notoginseng, a traditional Chinese medicine, as well as the synthesis and anticoagulant activity of a fucoidan (sulfated glycan derived from brown algae) library.

Lai-Xi Wang, PhD

University of Maryland

Topic: Synthesis and functional studies of selectively fluorinated N-glycans and antibodies

Fluorination has attracted considerable interest in recent years due to the unique physicochemical properties of fluorine, including its high electronegativity, small size, and ability to modulate molecular recognition and metabolic stability. Specifically, selectively fluorinated glycans can serve as valuable tools for probing glycan–protein interactions and for modulating the immunogenicity of carbohydrate antigens. Despite their potential, the synthesis of fluorinated N-glycans remains a significant challenge due to the complexity of glycan structures and the need for regio- and stereoselective incorporation of fluorine atoms. We describe in this conference the chemoenzymatic synthesis of selectively fluorinated high-mannose type and complex type N-glycans, and related HIV-1 glycopeptide antigens. In addition, the modified N-glycans were transferred to antibodies by an endoglycosynthase mutant to produce selectively fluorinated antibody glycoforms. The stability, antigenicity, and affinity for respective glycan-binding proteins of the fluorinated glycans and antibodies will be discussed.

Ulrika Westerlind, PhD

UMEA University, Sweden

Biao Yu, PhD

Shanghai Institute of Organic Chemistry, China

Topic: Synthesis and Biological Activities of Pregnane Glycosides

In this lecture, I shall highlight our recent work on (1) the glycosylation methods for the synthesis of 2-deoxy-β-pyranosidic linkages; (2) the total synthesis and structural revision of the pregnane 2,6-dideoxyglycosides from folk medicinal plants Ecdysanthera rosea and Chonemorpha megacalyx; and (3) the identifcation of the appetite-suppressing pregnane glycosides in Hoodia gordonii and their mechanisms of action.