DEVELOPMENT OF A FORMULATION WITH IMMUNOTHERAPEUTIC ACTIVITIES

• Grant number: 15/19547-5
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2016
• End date: September 30, 2018
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Celio Lopes Silva
• Grantee: Celio Lopes Silva
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Michelle Christiane Rodrigues Barbosa ; Wendy Martin Rios

Abstract

The proponent group of this project established in an unprecedented and successfully manner in Brazil, a technological platform that allowed the completion of the entire research and development chain of an immunomodulator based on a DNA plasmid encoding the mycobacterial Hsp65 protein gene (DNAhsp65). Existing studies contemplated from basic research and proof of concept, to the technological development, preclinical trials, including non-human primates, and clinical trial phase I/II. However, despite the excellent results obtained with the DNAhsp65 for immunotherapy of infectious diseases, autoimmune, allergic and cancer, there are important barriers to further development of this product and clinical use in the future. For the development of translational research that enables greater agility to take basic research knowledge to the market, the group aims in this project to study whether a probiotic bacterium, Lactococcus lactis expressing mycobacterial hsp65 (LLHsp65) can present immunogenicity and immunotherapeutic efficacy in experimental models of tuberculosis (TB), autoimmune disease (arthritis), cancer and allergy. It is expected that this new formulation LLHsp65 has immunomodulatory activity similar to, or better than, the one presented by DNAhsp65 and has significant advantages for translational research, among which we highlight: it can be administered orally, has good efficacy and immunogenic therapy for the control of these diseases, to stimulate mucosal and systemic immunity, does not contain adjuvants and endotoxins, easy to develop and produce in scale, low cost, good stability and easy acceptance by society. (AU)