Oncolytic Rhabdovirus Vaccine Boosts Chimeric Anti-DEC205 Priming for Effective Cancer Immunotherapy

Fanny Tzelepis; Harsimrat Kaur Birdi; Anna Jirovec; Silvia Boscardin; Christiano Tanese de Souza; Mohsen Hooshyar; Andrew Chen; Keara Sutherland; Robin J Parks; Joel Werier; Jean-Simon Diallo

doi:10.1016/j.omto.2020.10.007

Oncolytic Rhabdovirus Vaccine Boosts Chimeric Anti-DEC205 Priming for Effective Cancer Immunotherapy

Mol Ther Oncolytics. 2020 Oct 14:19:240-252. doi: 10.1016/j.omto.2020.10.007. eCollection 2020 Dec 16.

Authors

Fanny Tzelepis¹, Harsimrat Kaur Birdi^{1

2}, Anna Jirovec^{1

2}, Silvia Boscardin^{3

4}, Christiano Tanese de Souza¹, Mohsen Hooshyar¹, Andrew Chen¹, Keara Sutherland^{1

2}, Robin J Parks^{2

5}, Joel Werier⁶, Jean-Simon Diallo^{1

2}

Affiliations

¹ Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
² Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada.
³ Laboratory of Antigen Targeting to Dendritic Cells, Department of Parasitology, University of São Paulo, São Paulo, Brazil.
⁴ Institute for Investigation in Immunology (iii)-INCT, São Paulo, Brazil.
⁵ Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
⁶ Department of Surgery, The Ottawa Hospital, Ottawa, ON, Canada.

Abstract

Prime-boost vaccination employing heterologous viral vectors encoding an antigen is an effective strategy to maximize the antigen-specific immune response. Replication-deficient adenovirus serotype 5 (Ad5) is currently being evaluated clinically in North America as a prime in conjunction with oncolytic rhabdovirus Maraba virus (MG1) as a boost. The use of an oncolytic rhabdovirus encoding a tumor antigen elicits a robust anti-cancer immune response and extends survival in murine models of cancer. Given the prevalence of pre-existing immunity to Ad5 globally, we explored the potential use of DEC205-targeted antibodies as an alternative agent to prime antigen-specific responses ahead of boosting with an oncolytic rhabdovirus expressing the same antigen. We found that a prime-boost vaccination strategy, consisting of an anti-DEC205 antibody fused to the model antigen ovalbumin (OVA) as a prime and oncolytic rhabdovirus-OVA as a boost, led to the formation of a robust antigen-specific immune response and improved survival in a B16-OVA tumor model. Overall, our study shows that anti-DEC205 antibodies fused to cancer antigens are effective to prime oncolytic rhabdovirus-boosted cancer antigen responses and may provide an alternative for patients with pre-existing immunity to Ad5 in humans.

Keywords: Ad5; anti-DEC205; immunotherapy; oncolytic vaccine; prime-boost; rhabdovirus.