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Title: Pseudomonas aeruginosa type 3 secretion system mediated antigen delivery for cancer immunotherapy

Bertrand Toussaint

Univ.Grenoble Alpes, France

Biography

Pr Toussaint studied Biochemical Engineering at Polytechnique Institute of Toulouse (France). He received his PhD at Grenoble University in 1990. After one year post-doc supervised by Dr Vignais in Microbial Biochemistry (Grenoble) he started to learn medicine. He gets his MD in 2002. He works as practitioner in Clinical Chemistry at Grenoble University Hospital, is Professor of Medicine at University of Grenoble Alpes and is at the head of a research team called Experimental Recombinants Therapeutics at TIMC. He published 75 publications and is inventor of 5 patents.

Abstract

Live-attenuated bacterial vectors for antigens delivery have aroused growing interest in the field of cancer immunotherapy. Their potency to stimulate innate immunity and to promote intracellular antigen delivery into antigen-presenting cells could be exploited to elicit a strong and specific cellular immune response against tumor cells. We previously described genetically-modified and attenuated Pseudomonas aeruginosa vectors able to deliver in vivo protein antigens into antigen-presenting cells, through Type 3 secretion system of the bacteria. The latest attenuation process permits the bacteria to be metabolically active but unable to replicate so as no infection is possible (a process called “KBMA” : killed but metabolically active). Using this approach, we managed to protect immunized mice against aggressive B16 melanoma development in both a prophylactic and therapeutic setting. We further investigated the antigen-specific CD8+ T cell response, in terms of phenotypic and functional aspects, obtained after immunizations with a killed but metabolically active P. aeruginosa attenuated vector. We demonstrated that P. aeruginosa vaccine induces a highly functional pool of antigen-specific CD8+ T cell able to infiltrate the tumor. Furthermore, multiple immunizations allowed the development of a long-lasting immune response, represented by a pool of predominantly effector memory cells which protected mice against late tumor challenge. Overall, killed but metabolically active P. aeruginosa vector is a safe and promising approach for active and specific antitumor immunotherapy.
Audience take away:
• The concept of Live Biological Products
• The main bottlenecks for active and specific immunotherapy of cancer
• The ability of bacteria to deliver tumor antigens inside antigen presenting cells.
• The way to make a live bacteria  safe for a clinical use.