title: | Immune response to synthetic and natural tumor-associated carbohydrate antigens in patients with cancer: the specificity of IgG antibodies and their clinical significance |
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reg no: | ETF6726 |
project type: | Estonian Science Foundation research grant |
subject: |
3.1. Basic Medicine |
status: | accepted |
institution: | National Institute for Health Development |
head of project: | Oleg Kurtenkov |
duration: | 01.01.2006 - 31.12.2009 |
description: | Despite the fact that aberrant glycosylation profoundly affects the fundamental biological processes the glycomics has still received little attention in cancer research. Tumor-associated carbohydrate antigens (TACA) are overexpressed in multiple tumor types as a result of aberrant glycosylation. Cell-surface TACA can induce specific immune response in cancer patients suggesting they are promising targets for anticancer immunotherapy. Besides, a variable amounts of natural antibody to some TACA are present in every individual. Immune response to TACA, both natural and acquired, to be significant as prognostic factors for survival, metastasis, and invasion of cancer. However, many questions remain to be elucidated: the fine specificity of human anti-carbohydrate antibodies, their natural targets, the variations in health and disease, the impact of surgery, chemotherapy, changes during follow-up, and relation to the survival. Recently we described new unusual antibodies in patients with cancer which were specific to para-Forsman disaccharide (PFdi) and Tn-β. Aims: (i) the isolation of anti-PFdi, anti-Tnβ and anti-Gal IgG antibodies from patients with cancer by affinity chromatography and characterization of their specificity using a set of PAA-glycoconjugates, natural targets and monoclonal antibodies. (ii) the evaluation of the reactivity of antibodies (anti-TF, -Tn, -SiaTn, -Gal, Tnβ and -PFdi IgG) to natural targets (glycolipids and mucins) including tumor-derived antigens. (iii) to evaluate the clinical relevance of anti-carbohydrate epitope antibodies for diagnosis, monitoring and prognosis. We expect to characterize the fine specificity of human anticarbohydrate IgG antibodies to synthetic and natural ligands, and to select the tumor-related glycotopes of clinical importance. The data may be of value for increasing the sensitivity and specificity of cancer immunodiagnostics, the follow-up of patients with malignancy and for the optimization of chemo- and immunotherapy. |
project group | ||||
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no | name | institution | position | |
1. | Oleg Kurtenkov | Tervise Arengu Instituut | ||
2. | Ljudmila Miljuhhina | |||
3. | Jevgeni Smorodin |