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Thomas Kieber-Emmons, PhD Professor of Pathology, Microbiology, and Immunology Director of Basic Breast Cancer Research Josetta Wilkins Chair of Breast Cancer Research |
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Doctoral DegreeState University of New York at Buffalo, Biophysics Postdoctoral Training Roswell Park Memorial Institute, Molecular Immunology Research Interests Glycobiology Cancer Immunology
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| Cancer Vaccines | ||
| There are a variety of carbohydrates that have received attention as tumor antigens. These include gangliosides like GM2, GD2, GD3 expressed on melanomas, sarcomas and neuroblastomas, the Thomsen-Friedenreich antigen (TF), Tn and sialylated Tn (sTn) blood-group-related antigens that are expressed on mucins in a variety of epithelial cancers, fucosyl-GM1 expressed on small-cell lung cancers and the histo-blood group related Lewis antigens like Lewis Y and Globo H antigens also expressed on a variety of epithelial cancers. The restricted distribution of these antigens on normal tissues and their expression on malignancies suggest that these carbohydrate antigens are important targets for immunotherapy. Carbohydrate antigens however are T cell independent antigens. As such, they function as poor immunogens. As a means to convert carbohydrate T independent responses to T dependent responses we are pioneering the development of peptides that function as carbohydrate mimics. We have developed peptides that mimic bacterial, viral and tumor associated carbohydrates using a combination of screening random peptide display libraries and molecular modeling (structure assisted vaccine design). In this regard we have shown that it is possible to define peptides theoretically using computer-based approaches (bioinformatics) that validate those identified experimentally.
In terms of cancer vaccines, we are focusing on antigens associated with Breast, ovarian, colon, small cell lung cancers and melanoma. Peptides that mimic carbohydrate structure have significant advantages as vaccines. We have shown that peptide mimetic immunization leads to 1.) Consistently high titer tumor reactive IgM and IgG serum antibodies. 2.) Serum antibodies that mediate complement lysis of tumor cells in vitro. 3.) Serum antibodies that mediate the killing of target cells in xenografted animals. 4.) Serum antibodies that do not cross-reactive with normal tissues. and 5) activation of tumor reactive cellular responses in both prophylactic and therapeutic settings. Consequently, this approach constitutes a novel strategy in vaccine design for further reducing micrometastases and prevention of recurrence. We are moving toward testing these peptides in pilot trials in humans in the very near future. | ||
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