Standing
Undergraduate
Type of Proposal
Oral Research Presentation
Faculty
Faculty of Science
Faculty Sponsor
John F. Trant
Proposal
Cancer vaccines are a promising approach to cancer treatment by activating the immune system towards cancer cells. The challenge, however, comes with the identification of biomarkers correlated with cancer. Unfortunately, many oncotargets are simply upregulated in cancer; these are inappropriate vaccine targets as they are also present on healthy cells and therefore would ultimately initiate a very dangerous systemic immune response. In contrast, Tumor-Associated Carbohydrate Antigens (TACAs) are not found in healthy adult tissue but are found on over 90% of biopsied carcinomas. When incorporated into glycopeptides or other immunogenic scaffolds, these carbohydrate antigens have formed the basis of the development of anti-tumor immunotherapies through the induction of a specific immune response against cancer cells. However, despite promising preliminary data, none of these candidates have reached the clinic. Our hypothesis is that the carbohydrates on the vaccines may not survive antigen processing, and so more stable versions of these materials are required to create viable vaccines.
Our approach is to incorporate TACAs lacking the labile glycosidic bond: acetal-free carbohydrates (AFCs). This project aims to remove the unstable acetal functional group to yield a more robust carbohydrate structure that can then be incorporated into a vaccine candidate. In this presentation, two synthetic pathways will be described: conversion of a carbohydrate to a carbasugar through a rearrangement, and de novo synthesis from noncarbohydrate materials.
Availability
March 29: 12-3pm March 30: 12-1pm March 31: 12-1:20pm April 1: 12-3pm
Toward the synthesis of an acetal-free Tn antigen anti-cancer vaccine candidate
Cancer vaccines are a promising approach to cancer treatment by activating the immune system towards cancer cells. The challenge, however, comes with the identification of biomarkers correlated with cancer. Unfortunately, many oncotargets are simply upregulated in cancer; these are inappropriate vaccine targets as they are also present on healthy cells and therefore would ultimately initiate a very dangerous systemic immune response. In contrast, Tumor-Associated Carbohydrate Antigens (TACAs) are not found in healthy adult tissue but are found on over 90% of biopsied carcinomas. When incorporated into glycopeptides or other immunogenic scaffolds, these carbohydrate antigens have formed the basis of the development of anti-tumor immunotherapies through the induction of a specific immune response against cancer cells. However, despite promising preliminary data, none of these candidates have reached the clinic. Our hypothesis is that the carbohydrates on the vaccines may not survive antigen processing, and so more stable versions of these materials are required to create viable vaccines.
Our approach is to incorporate TACAs lacking the labile glycosidic bond: acetal-free carbohydrates (AFCs). This project aims to remove the unstable acetal functional group to yield a more robust carbohydrate structure that can then be incorporated into a vaccine candidate. In this presentation, two synthetic pathways will be described: conversion of a carbohydrate to a carbasugar through a rearrangement, and de novo synthesis from noncarbohydrate materials.