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