2284P - Pre-clinical assessment of the therapeutic potential of a CD80-Fc-armed oncolytic virus (VSV-GP-CD80Fc)

Background

Oncolytic viruses (OVs) are capable of eradicating tumor cells and eliciting antitumoral immunity, thus, virotherapy is a promising approach in the field of novel IO-mediated therapies. VSV-GP is an OV which can mediate potent oncolysis in a broad range of solid cancer cell types and initiate adaptive anti-cancer immunity. It exhibits minimal ecotoxicity, as measured by low or absent shedding of infectious virus, poor tenacity in the environment, and no evidence for pathogenesis in treated livestock (healthy swine model). Based on this data, VSV-GP is currently in first-in-human Phase I trial (NCT05155332). VSV-GP-CD80Fc is a variant of VSV-GP that encodes for a human CD80-Fc fusion protein. The immune-promoting cargo of VSV-GP-CD80Fc was chosen to provide co-stimulation to intra-tumoral T cells. Secreted CD80-Fc exerts its mode of action by binding to CD28 (agonistic) on T cells, which stimulates them in a Fc/Fcγ receptor (FcγR)-dependent manner.

Methods

A pre-clinical characterization of VSV-GP-CD80Fc’s replication competence, cargo-expression and therapeutic potential was conducted using state-of-the-art in vitro and in vivo analyses.

Results

The results revealed comparable replication kinetics and an equally good oncolytic activity compared with its antecessor virus, VSV-GP. Furthermore, in vivo mode-of-action studies confirmed the immune-stimulatory effect of the cargo fusion protein. In efficacy studies of the mouse syngeneic CT26.CL25-INFAR-/- model, tumor growth inhibition and survival were dose-dependent leading to >90% tumor growth inhibition in the groups with the highest virus dose, independent of the route of administration. Tumor growth profiles derived from the aforementioned studies were used to characterize the onset of pharmacological activity and to derive a dose prediction that results in an estimated pharmacological active dose (PAD) for VSV-GP-CD80Fc in humans. This can be used as a basis for the definition of a first in human (FIH) starting dose.

Conclusions

In conclusion, VSV-GP-CD80Fc is a highly potent and efficacious oncolytic virus. The usage of the CD80-Fc cargo further boosts the therapeutic potential of VSV-GP-based treatments in humans.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Boehringer Ingelheim Pharma GmbH & Co. KG.

Funding

Boehringer Ingelheim Pharma GmbH & Co. KG.

Disclosure

A. Ackermann, P. Erlmann, V.L. Herrmann, J. Petschenka, B. Stierstorfer, J. Wojtyniak, J. Rippmann: Financial Interests, Personal, Other, Employee: Boehringer Ingelheim Pharma GmbH & Co. KG. D. Hotter: Financial Interests, Personal, Principal Investigator, Employee: Boehringer Ingelheim Pharma GmbH & Co. KG. S. Mostböck: Financial Interests, Personal, Other, Employee: Boehringer Ingelheim RCV. T. Nolden: Financial Interests, Personal, Principal Investigator, Employee: ViraTherapeutics GmbH. T. Schönberger: Financial Interests, Personal, Principal Investigator, Employee: Boehringer Ingelheim Pharma GmbH & Co. KG. K. Elbers: Financial Interests, Personal, Other, Employee: ViraTherapeutics. P. Mueller: Financial Interests, Personal, Other, Employee: BI Venture Fund.