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

• Հիմնական հեղինակներ: Mathilde Bausart (Հեղինակ), Kevin Vanvarenberg (Հեղինակ), Bernard Ucakar (Հեղինակ), Alessandra Lopes (Հեղինակ), Gaëlle Vandermeulen (Հեղինակ), Alessio Malfanti (Հեղինակ), Véronique Préat (Հեղինակ)
• Ձևաչափ: Գիրք
• Հրապարակվել է: MDPI AG, 2022-05-01T00:00:00Z.
• Խորագրեր: article
• Առցանց հասանելիություն: Connect to this object online.

Ամփոփում

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.

Նյութի նկարագրություն

10.3390/pharmaceutics14051025
1999-4923