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Development of recombinant Bacillus Calmette-Guerin in tumor immunotherapy

Grant number: 17/01921-3
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): June 01, 2017
Effective date (End): December 31, 2017
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Luciana Cezar de Cerqueira Leite
Grantee:Kauan Ribeiro de Sena Gomes
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Recombinant Bacillus Calmette-Guérin (rBCG) is one of the most widely used vaccine vectors in the world because of its great adjuvant power and ability to elicit a prolonged immune response. Molecular biology techniques have allowed the construction of bacilli with non-self antigens capable of directing the immune response to profiles more suited to fighting diseases and pathogens such as tuberculosis and bladder cancer. These diseases require a response with a more Th1 profile to achieve a better therapeutic outcome. By studying the level of antigen expression and its effect on the immune response, with the increase of Th1 cytokines such as IFN-³ and IL-2, it is possible to produce more specific and better performing recombinant vaccines capable of exploring the immunotherapeutic potential of immune targeting in disease control. The present project aims at the construction of recombinant bacilli capable of expressing an adjuvant molecule, the A subunit of the E.coli heat-labile enterotoxin (LTAK63), under the control of a library of promoters with different expression forces, to evaluate the effect of the level of expression in the immunotherapeutic potential of these bacilli against bladder cancer cell models. The objective is to evaluate the effect of the antigen expression force on the therapeutic performance against bladder cancer cells. The study may provide information capable of integrating molecular expression levels with modulation of the antitumor response to initiate an analysis following a systems approach.