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Content archived on 2024-06-18

Creation, evaluation and characterization of the ideal bioprobe for the cancer antigen Tn by improved selection of mutant lectins from phage display libraries

Objective

Major changes in carbohydrate expression occur during the onset and progression of cancer. These alterations in glycosylation may result in both the loss of normal carbohydrate antigens (e.g. ABO blood group antigens) and/or high expression of carbohydrate structures that normally have low or restricted expression in healthy adults.
The Tn antigen is expressed in most carcinomas, during embryogenesis, on pathogenic parasites, and on HIV, yet its expression is rare in normal adult tissue, creating a considerable interest in monitoring the expression of the Tn antigen for diagnostic purposes as well as for the development of Tn-based vaccines for cancer and HIV. The accurate detection of the Tn antigen is essential for both basic and applied research. However, monitoring the expression of this antigen is not trivial. Selective recognition of carbohydrate epitopes is challenging, especially for small epitopes such as the Tn antigen, and presently, there is no method nor approach providing an accurate and reliable information on the expression of this antigen.

The goal of present proposal is to “evolve” the GafD lectin as a molecular probe to be used in the detection the Tn tumor biomarker and solve the problem of its recurrent inaccurate detection in cancer. Phage display technology will be used to modulate the properties of GafD throughout rounds of selection against different antigens, accumulating and refining its improvements in selectivity/affinity towards a finely tuned and specific Tn antigen binder. Subsequently, the identified receptor(s) will be expressed and fully characterized by an integrated multidisciplinary approach compressed of glycan microarrays, NMR; ITC; SPR and X-ray crystallography.
The presented research will create a defined, precise and reliable tool for the evaluation of Tn expression, which will have great implications in the development of Tn-based diagnostics and vaccines.

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Topic(s)

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Call for proposal

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FP7-PEOPLE-2011-IOF
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Funding Scheme

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MC-IOF - International Outgoing Fellowships (IOF)

Coordinator

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
EU contribution
€ 225 615,75
Address
RUE MICHEL ANGE 3
75794 PARIS
France

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Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
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Total cost

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