Abstract

Tumor-associated carbohydrate antigens (TACAs) are saccharides and oligosaccharides which show highly restricted expression on cancer cells. Since TACAs are unique to cancer cells, there is a great interest in generating an active immune response against TACAs as a means of reducing cancer metastasis or recurrence. TACAs are also useful biomarkers for evaluating the aggressiveness of the cancer. Two major challenges to using TACAs in active immunotherapy are their poor antigenicity and the inherent difficulty of synthesizing oligosaccharides and related glycoconjugates by chemical means. This application proposes to synthesize and study the antigenicity of TACA glycoconjugates. A key aspect of the proposal is the study of increased vaccine antigenicity mediated by xenobiotic carbohydrates unrelated to the TACAs. The xenobiotic carbohydrates are proposed to enhance antigenicity through anti- carbohydrate antibody-mediated mechanisms. This proposal takes advantage of a collaborative interaction between PIs trained in organic chemistry and immunology so that the antigenicity of all vaccines will be well characterized in mice.

Public Health Relevance

This project will develop and evaluate the cellular and humor immune response of vaccines in mice that will serve as leads for human anti-cancer vaccines. Chemical approaches will be developed that will aid in generating diagnostic and therapeutic agents for the treatment of cancer.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
1R15GM094734-01A1
Application #
8101525
Study Section
Synthetic and Biological Chemistry A Study Section (SBCA)
Program Officer
Fabian, Miles
Project Start
2011-05-01
Project End
2014-04-30
Budget Start
2011-05-01
Budget End
2014-04-30
Support Year
1
Fiscal Year
2011
Total Cost
$334,651
Indirect Cost

  Institution

Name
University of Toledo
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
051623734
City
Toledo
State
OH
Country
United States
Zip Code
43606

  Publications

Vartak, Abhishek; Hefny, Fatma M; Sucheck, Steven J (2018) Synthesis of Oligosaccharide Components of the Outer Core Domain of P. aeruginosa Lipopolysaccharide Using a Multifunctional Hydroquinone-Derived Reducing-End Capping Group. Org Lett 20:353-356
Hossain, Md Kamal; Vartak, Abhishek; Karmakar, Partha et al. (2018) Augmenting Vaccine Immunogenicity through the Use of Natural Human Anti-rhamnose Antibodies. ACS Chem Biol 13:2130-2142
Vartak, Abhishek; Sucheck, Steven J (2016) Recent Advances in Subunit Vaccine Carriers. Vaccines (Basel) 4:
Hossain, Md Kamal; Wall, Katherine A (2016) Immunological Evaluation of Recent MUC1 Glycopeptide Cancer Vaccines. Vaccines (Basel) 4:
Karmakar, Partha; Lee, Kyunghee; Sarkar, Sourav et al. (2016) Synthesis of a Liposomal MUC1 Glycopeptide-Based Immunotherapeutic and Evaluation of the Effect of l-Rhamnose Targeting on Cellular Immune Responses. Bioconjug Chem 27:110-20
Long, David E; Karmakar, Partha; Wall, Katherine A et al. (2014) Synthesis of ?-L-rhamnosyl ceramide and evaluation of its binding with anti-rhamnose antibodies. Bioorg Med Chem 22:5279-89
Bouhall, Samantha K; Sucheck, Steven J (2014) In situ preactivation strategies for the expeditious synthesis of oligosaccharides: A review. J Carbohydr Chem 33:347-367
Gaitonde, Vishwanath; Lee, Kyunghee; Kirschbaum, Kristin et al. (2014) Bio-Based Bisfuran: Synthesis, Crystal Structure and Low Molecular Weight Amorphous Polyester. Tetrahedron Lett 55:4141-4145
Sarkar, Sourav; Salyer, Alex C D; Wall, Katherine A et al. (2013) Synthesis and immunological evaluation of a MUC1 glycopeptide incorporated into l-rhamnose displaying liposomes. Bioconjug Chem 24:363-75
Ibrahim, Diaa A; Boucau, Julie; Lajiness, Daniel H et al. (2012) Design, synthesis, and X-ray analysis of a glycoconjugate bound to Mycobacterium tuberculosis antigen 85C. Bioconjug Chem 23:2403-16

Showing the most recent 10 out of 12 publications