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Modulation of anti-tumor, CD8-mediated immune response by genetically modified infectious agents

Grant number: 18/01627-0
Support type:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): June 01, 2018
Effective date (End): March 31, 2019
Field of knowledge:Biological Sciences - Immunology
Principal Investigator:João Gustavo Pessini Amarante Mendes
Grantee:Aamir Rana
Supervisor abroad: Subash Sad
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Local de pesquisa : University of Ottawa (uOttawa), Canada  
Associated to the scholarship:15/12977-4 - Modulation of anti-tumor immune response by genetically modified infectious agents, BP.DR

Abstract

Effective immunotherapy against cancer requires efficient immune responses. The weak immunogenic characteristic of tumor cells contributes to their evasion from immune system. To overcome this, adjuvant signals that promote an inflammatory environment have been proposed as an approach to enhance the antigenicity of tumor cells. Preferential accumulation of pathogenic bacteria in the tumor microenvironment may offer a great potential for cancer immunotherapy. Ovalbumin (OVA)-expressing Listeria monocytogenes (LM) has been used to boost anti-cancer immune response in mouse models of orthotopic OVA-expressing tumors. Although, the role of cell death mechanisms in regulating immune response against intracellular bacteria have been intensively investigated their contribution to the adjuvant effect of LM vectors in the context of cancer immunotherapy remains obscure. We aim to evaluate the role of necroptosis and pyroptosis in the modulation of antigen specific anti-tumor and CD8+T cell response. We will use LM-OVA for immunization/infection of Ripk3, Casp-1 and Ripk3, Casp-1 double deficient mice to observe the effect of Ripk-3 and Casp-1 individual and combined deficiency in the modulation of antigen specific anti-tumor and anti-CD8+T cell response.