Abstract

In this application the investigator proposes to examine the use of Ley and globo H carbohydrate antigens as vaccines for the possible therapy of ovarian epithelial cancer.
The aims are: 1) to synthesize Ley and globo H oligosaccaharides and to couple them to carrier proteins. 2) to pursue preclinical immunogenicity studies on these antigens to determine the best conjugates and most effective adjuvant to induce an antibody response reacting with tumor cells and 3) to possibly extend these studies to a clinical trial in high risk ovarian cancer patients to determine if an antibody response can be obtained in humans.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA071506-04
Application #
2895596
Study Section
Experimental Immunology Study Section (EI)
Program Officer
Yovandich, Jason L
Project Start
1996-09-01
Project End
2001-06-30
Budget Start
1999-07-01
Budget End
2000-06-30
Support Year
4
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065

  Publications

Kudryashov, V; Glunz, P W; Williams, L J et al. (2001) Toward optimized carbohydrate-based anticancer vaccines: epitope clustering, carrier structure, and adjuvant all influence antibody responses to Lewis(y) conjugates in mice. Proc Natl Acad Sci U S A 98:3264-9
Sabbatini, P J; Kudryashov, V; Ragupathi, G et al. (2000) Immunization of ovarian cancer patients with a synthetic Lewis(y)-protein conjugate vaccine: a phase 1 trial. Int J Cancer 87:79-85
Wang, Z G; Williams, L J; Zhang, X F et al. (2000) Polyclonal antibodies from patients immunized with a globo H-keyhole limpet hemocyanin vaccine: isolation, quantification, and characterization of immune responses by using totally synthetic immobilized tumor antigens. Proc Natl Acad Sci U S A 97:2719-24
Ragupathi, G; Howard, L; Cappello, S et al. (1999) Vaccines prepared with sialyl-Tn and sialyl-Tn trimers using the 4-(4-maleimidomethyl)cyclohexane-1-carboxyl hydrazide linker group result in optimal antibody titers against ovine submaxillary mucin and sialyl-Tn-positive tumor cells. Cancer Immunol Immunother 48:1-8
Slovin, S F; Ragupathi, G; Adluri, S et al. (1999) Carbohydrate vaccines in cancer: immunogenicity of a fully synthetic globo H hexasaccharide conjugate in man. Proc Natl Acad Sci U S A 96:5710-5
Kudryashov, V; Ragupathi, G; Kim, I J et al. (1998) Characterization of a mouse monoclonal IgG3 antibody to the tumor-associated globo H structure produced by immunization with a synthetic glycoconjugate. Glycoconj J 15:243-9
Ragupathi, G; Koganty, R R; Qiu, D et al. (1998) A novel and efficient method for synthetic carbohydrate conjugate vaccine preparation: synthesis of sialyl Tn-KLH conjugate using a 4-(4-N-maleimidomethyl) cyclohexane-1-carboxyl hydrazide (MMCCH) linker arm. Glycoconj J 15:217-21
Kudryashov, V; Kim, H M; Ragupathi, G et al. (1998) Immunogenicity of synthetic conjugates of Lewis(y) oligosaccharide with proteins in mice: towards the design of anticancer vaccines. Cancer Immunol Immunother 45:281-6
Zhang, S; Zhang, H S; Cordon-Cardo, C et al. (1997) Selection of tumor antigens as targets for immune attack using immunohistochemistry: II. Blood group-related antigens. Int J Cancer 73:50-6