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Article

Combination of DNA Vaccine and Immune Checkpoint Blockades Improves the Immune Response in an Orthotopic Unresectable Glioblastoma Model

Advanced Drug Delivery and Biomaterials, Louvain Drug Research Institute, UCLouvain, 1200 Brussels, Belgium
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Academic Editor: Urska Kamensek
Pharmaceutics 2022, 14(5), 1025; https://doi.org/10.3390/pharmaceutics14051025
Received: 25 March 2022 / Revised: 4 May 2022 / Accepted: 6 May 2022 / Published: 10 May 2022
(This article belongs to the Special Issue Plasmid DNA for Gene Therapy and DNA Vaccine Applications)
Combination immunotherapy has emerged as a promising strategy to increase the immune response in glioblastoma (GBM) and overcome the complex immunosuppression occurring in its microenvironment. In this study, we hypothesized that combining DNA vaccines—to stimulate a specific immune response—and dual immune checkpoint blockade (ICB)—to decrease the immunosuppression exerted on T cells—will improve the immune response and the survival in an orthotopic unresectable GL261 model. We first highlighted the influence of the insertion position of a GBM epitope sequence in a plasmid DNA vaccine encoding a vesicular stomatitis virus glycoprotein (VSV-G) (here referred to as pTOP) in the generation of a specific and significant IFN-γ response against the GBM antigen TRP2 by inserting a CD8 epitope sequence in specific permissive sites. Then, we combined the pTOP vaccine with anti-PD-1 and anti-CTLA-4 ICBs. Immune cell analysis revealed an increase in effector T cell to Treg ratios in the spleens and an increase in infiltrated IFN-γ-secreting CD8 T cell frequency in the brains following combination therapy. Even if the survival was not significantly different between dual ICB and combination therapy, we offer a new immunotherapeutic perspective by improving the immune landscape in an orthotopic unresectable GBM model. View Full-Text
Keywords: glioblastoma; plasmid DNA vaccine; immune checkpoint blockade; combination immunotherapy glioblastoma; plasmid DNA vaccine; immune checkpoint blockade; combination immunotherapy
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MDPI and ACS Style

Bausart, M.; Vanvarenberg, K.; Ucakar, B.; Lopes, A.; Vandermeulen, G.; Malfanti, A.; Préat, V. Combination of DNA Vaccine and Immune Checkpoint Blockades Improves the Immune Response in an Orthotopic Unresectable Glioblastoma Model. Pharmaceutics 2022, 14, 1025. https://doi.org/10.3390/pharmaceutics14051025

AMA Style

Bausart M, Vanvarenberg K, Ucakar B, Lopes A, Vandermeulen G, Malfanti A, Préat V. Combination of DNA Vaccine and Immune Checkpoint Blockades Improves the Immune Response in an Orthotopic Unresectable Glioblastoma Model. Pharmaceutics. 2022; 14(5):1025. https://doi.org/10.3390/pharmaceutics14051025

Chicago/Turabian Style

Bausart, Mathilde, Kevin Vanvarenberg, Bernard Ucakar, Alessandra Lopes, Gaëlle Vandermeulen, Alessio Malfanti, and Véronique Préat. 2022. "Combination of DNA Vaccine and Immune Checkpoint Blockades Improves the Immune Response in an Orthotopic Unresectable Glioblastoma Model" Pharmaceutics 14, no. 5: 1025. https://doi.org/10.3390/pharmaceutics14051025

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