Phenotypic and functional analysis of innate immune response cells from bladder cancer patients as a proof of concept for the immunostimulatory effect of recombinant BCG

• Grant number: 24/12935-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: January 01, 2025
• End date: August 31, 2028
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Ana Carolina Ramos Moreno
• Grantee: Matheus Ferreira de Almeida
• Host Institution: Instituto Butantan. São Paulo , SP, Brazil
• Associated research grant: 23/02577-5 - Study of the mechanisms responsible for trained immunity induced by Bacillus Calmette-Guérin (BCG) in infectious diseases and Cancer, AP.TEM

Abstract

Cancer treatment has always been a challenge, as local and systemic tumor factors create a complex microenvironment that generates a set of signals impacting infiltrating immune cells. For instance, peripheral blood monocytes from cancer patients tend to transform into immunosuppressive antigen-presenting cells (APCs), where soluble factors "educate" immune cells not to activate efficiently to combat the cancer. Moreover, the metabolic plasticity of the tumor environment often affects the efficacy of therapeutic procedures, including those based on immunological tools. Effective immunotherapy can reprogram immune cells, potentially leading to tumor remission. Therefore, understanding activation and immunosuppression pathways is crucial in Immuno-Oncology to advance the development of new therapeutic approaches against cancer.The Vaccine Development Laboratory at the Butantan Institute has expertise in developing vaccines based on recombinant Bacillus Calmette-Guérin (rBCG), which have shown promising therapeutic potential in experimental models of bladder cancer. Two rBCG strains, rBCG-S1PT and rBCG-LTAK63, have demonstrated therapeutic efficacy in preclinical studies of bladder cancer, inducing more effective immune responses compared to native BCGs. Our next step, and the objective of the present proposal, involves translational research in partnership with the Cancer Institute of the State of São Paulo (ICESP), aiming to evaluate the immunostimulatory potential of these strains in innate immune cells from bladder cancer patients. This study may open new therapeutic perspectives and strengthen Brazil's position at the forefront of cancer immunotherapy research.