Poly-functional and long-lasting anticancer immune response elicited by a safe attenuated Pseudomonas aeruginosa vector for antigens delivery

Xavier Chauchet (1, 2) , Dalil Hannani (2) , Sophia Djebali (3) , David Laurin (1, 4) , Benoit Polack (1, 5, 6) , Jacqueline Marvel (3) , Laurent Buffat (2) , Bertrand Toussaint (1, 7) , Audrey Le Gouellec (1, 7)

1 TIMC-IMAG-TheREx - Thérapeutique Recombinante Expérimentale
2 APCure
3 Immunité et lymphocytes cytotoxiques – Immunity and cytotoxic lymphocytes
4 Hôpital Michallon
5 Laboratoire d'hématologie
6 Clinique Universitaire d'Hématologie [La Tronche, Grenoble]
7 Laboratoire de Biochimie des Enzymes et des Protéines

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. Using this approach, we managed to protect immunized mice against aggressive B16 melanoma development in both a prophylactic and therapeutic setting. In this study, 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.

Domaines: Biotechnologie; Immunothérapie; Cancer

Xavier Chauchet, Dalil Hannani, Sophia Djebali, David Laurin, Benoit Polack, et al.. Poly-functional and long-lasting anticancer immune response elicited by a safe attenuated Pseudomonas aeruginosa vector for antigens delivery. Molecular Therapy - Oncolytics, 2016, 3, pp.16033. ⟨10.1038/mto.2016.33⟩. ⟨hal-01571680⟩