Moving innovative oncolytic virus-based therapies into the clinic

Oncolytic viruses (OVs) are of growing interest as cancer therapeutics for their ability to kill tumour cells both directly by inducing oncolysis and indirectly by activating antitumour immune responses.
Our team has unique scientific and clinical expertise in protoparvoviruses (PV) which belong to the dozen of oncolytic viruses presently evaluated at both preclinical and clinical levels. While PV share anticancer properties with other OVs, they distinguish themselves by their natural (i.e. non engineered) oncoselectivity, and their small size (nanoparticles) allowing them to reach and disseminate in tumours protected by physiological barriers (e.g. brain blood barrier). One PV, parvovirus H-1 (H-1PV), has been tested in a phase I/IIa clinical trial in patients with recurrent glioblastoma multiforme (GBM), showing safety and first promising signs of efficacy. However, further development is necessary to improve clinical outcome.
The rationale of the present proposal is to take advantage of intrinsic properties of PVs and other OVs to devise novel strategies for the development of second generation PVs and PV-based combinatorial treatments (combination with other clinically approved drugs and/or immune checkpoint antibodies) with enhanced anticancer efficacy. The project is more particularly based on our recent pioneering studies, paving the way for a strategy that is, to the best of our knowledge, unique in the oncolytic virus field: the generation of chimeric viruses which combine the advantages and circumvent the limitations of two distinct oncolytic viruses, namely adenovirus and PV. In conclusion, this research program is expected to generate and validate (proofs of concept) a portfolio of novel PVs, derivatives thereof and clinical protocols. Given the fact that the wild type virus showed first signs of efficacy in cancer patients, we trust that the development of the hereby proposed novel PV-based anticancer strategies may provide a key to the success of PVs in clinical settings.