| Grant number: | 13/17224-9 |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| Start date: | November 01, 2013 |
| End date: | January 31, 2017 |
| Field of knowledge: | Biological Sciences - Genetics - Human and Medical Genetics |
| Principal Investigator: | Sang Won Han |
| Grantee: | Bianca Ferrarini Zanetti |
| Host Institution: | Centro de Terapia Celular e Molecular. Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil |
Abstract Cancer is a major public health problem in the world, and in 2008 approximately 13% of global deaths were due to this group of diseases. Some cancers, such as tumors of the digestive system, breast, lung and thyroid possess, between several similarities, the overexpression of a glycoprotein, the carcinoembryonic antigen (CEA). Also expressed in epithelia, especially during embryonic development, CEA has various biological functions, such as adhesion, regulation of signal transduction, receptor internalization and inhibition of cell death. As CEA is seen by the immune system as self-protein, patients with CEA-positive tumors do not develop immune response against this tumor marker. Thus, the challenge of this work is to research a way to break immune tolerance to CEA and induce humoral and cellular responses against this antigen by DNA vaccination. In our previous studies, a monoclonal anti-idiotypic antibody to CEA, mAb 6.C4, was generated and DNA sequences which correspond to the variable regions of this antibody were isolated and used to construct scFv (single chain Fragment variable) 6.C4, which was able to break immune tolerance and induce the generation of immune response in vivo against a CEA transgenic animal model for CEA. However, this preventive vaccine has not able to fully contain tumor progression. For this vaccine to become efficient enough to eliminate tumors already present or prevent tumor progression introduced, it's needed a good enhancement of gene vaccination with scFv 6.C4, which will be held with adjuvants / activators of the immune system, like cytokines such as IL -2, IL-12 and GM-CSF, fragment C of tetanus toxin or adenovirus expressing CEA alone as well as alone as in combined vaccine regimens. | |
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