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

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 oncoly...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2020-12-01
Series:Molecular Therapy: Oncolytics
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2372770520301583
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author 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
author_facet 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
author_sort Fanny Tzelepis
collection DOAJ
description 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.
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spelling doaj.art-85c0f1ffc30c4c7e93249fbf227e89f32022-12-21T18:26:03ZengElsevierMolecular Therapy: Oncolytics2372-77052020-12-0119240252Oncolytic Rhabdovirus Vaccine Boosts Chimeric Anti-DEC205 Priming for Effective Cancer ImmunotherapyFanny Tzelepis0Harsimrat Kaur Birdi1Anna Jirovec2Silvia Boscardin3Christiano Tanese de Souza4Mohsen Hooshyar5Andrew Chen6Keara Sutherland7Robin J. Parks8Joel Werier9Jean-Simon Diallo10Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON, CanadaCentre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, CanadaCentre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, CanadaLaboratory of Antigen Targeting to Dendritic Cells, Department of Parasitology, University of São Paulo, São Paulo, Brazil; Institute for Investigation in Immunology (iii)-INCT, São Paulo, BrazilCentre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON, CanadaCentre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON, CanadaCentre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON, CanadaCentre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, CanadaDepartment of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada; Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON, CanadaDepartment of Surgery, The Ottawa Hospital, Ottawa, ON, CanadaCentre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada; Corresponding author: Jean-Simon Diallo, Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, 501 Smyth Road, C3128, Ottawa, ON K1H8L6, Canada.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.http://www.sciencedirect.com/science/article/pii/S2372770520301583anti-DEC205rhabdovirusoncolytic vaccineAd5prime-boostimmunotherapy
spellingShingle 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
Oncolytic Rhabdovirus Vaccine Boosts Chimeric Anti-DEC205 Priming for Effective Cancer Immunotherapy
Molecular Therapy: Oncolytics
anti-DEC205
rhabdovirus
oncolytic vaccine
Ad5
prime-boost
immunotherapy
title Oncolytic Rhabdovirus Vaccine Boosts Chimeric Anti-DEC205 Priming for Effective Cancer Immunotherapy
title_full Oncolytic Rhabdovirus Vaccine Boosts Chimeric Anti-DEC205 Priming for Effective Cancer Immunotherapy
title_fullStr Oncolytic Rhabdovirus Vaccine Boosts Chimeric Anti-DEC205 Priming for Effective Cancer Immunotherapy
title_full_unstemmed Oncolytic Rhabdovirus Vaccine Boosts Chimeric Anti-DEC205 Priming for Effective Cancer Immunotherapy
title_short Oncolytic Rhabdovirus Vaccine Boosts Chimeric Anti-DEC205 Priming for Effective Cancer Immunotherapy
title_sort oncolytic rhabdovirus vaccine boosts chimeric anti dec205 priming for effective cancer immunotherapy
topic anti-DEC205
rhabdovirus
oncolytic vaccine
Ad5
prime-boost
immunotherapy
url http://www.sciencedirect.com/science/article/pii/S2372770520301583
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