Malignant brain tumors cause severe neurological deficits and are associated with poor prognosis and high recurrence rates despite significant advances in brain cancer therapy. Pet animals are frequently affected by similar brain cancer types as humans and have been recently recognized to be a powerful translational model for cancer therapy research. We strive to harness the neuroinfectious pathogens we study (canine distemper virus (CDV), Listeria monocytogenes) to provide a microbial immunotherapy platform for brain cancer-immunotherapy in dogs and cats. This platform aims at fighting brain cancer at different levels by combining synergistic immunotherapeutic approaches: ( i ) the rearming of the antitumoral immune response by vaccination with Listeria monocytogenes delivering tumor-associated antigens (TAA) triggering the peripheral education and amplification of antitumoral CD8+ T-lymphocytes, (ii) the induction of immunogenic cell death (ICD) of cancer cells via engineered oncolytic CDV triggering tumor infiltration with CD8+ T-lymphocytes (iii) the direct delivery of immune checkpoint inhibitors into the tumor microenvironment via the oncolytic CDV vector.
In cooperation with the Institute of Parasitology (group Andrew Hemphill, https://www.ipa.vetsuisse.unibe.ch/about_us/personen/prof_dr_phil_nat_hemphill_andrew/index_eng.html ), we tested our Listeria monocytogenes vaccine vector Lm3Dx in preclinical models for safety and efficacy against infection with the protozoa Neospora caninum. These proof-of-principle experiments showed that vaccination with Lm3Dx expressing Neospora antigens provides protection against vertical transmission and brain infection. These results encourage us to translate the treatment of brain tumors in pets. Currently we screen tumors for suitable targets.
Safety of a Novel Listeria monocytogenes -Based Vaccine Vector Expressing NcSAG1 ( Neospora caninum Surface Antigen Pownall WR, Imhof D, Trigo NF, Ganal-Vonarburg SC, Plattet P, Monney C, Forterre F, Hemphill A, Oevermann A. Front Cell Infect Microbiol . 2021 Aug 25;11:675219.
doi : 10.3389/fcimb.2021.675219. eCollection 2021.