A Novel Chimeric Oncolytic Virus Mediates a Multifaceted Cellular Immune Response in a Syngeneic B16 Melanoma Model.

Autor: Glauß S; Department of Internal Medicine II, Rechts der Isar Hospital, Technical University of Munich, 81675 Munich, Germany., Neumeyer V; Department of Internal Medicine II, Rechts der Isar Hospital, Technical University of Munich, 81675 Munich, Germany., Hanesch L; Department of Internal Medicine II, Rechts der Isar Hospital, Technical University of Munich, 81675 Munich, Germany., Marek J; Department of Internal Medicine II, Rechts der Isar Hospital, Technical University of Munich, 81675 Munich, Germany., Hartmann N; Department of Internal Medicine II, Rechts der Isar Hospital, Technical University of Munich, 81675 Munich, Germany., Wiedemann GM; Department of Internal Medicine II, Rechts der Isar Hospital, Technical University of Munich, 81675 Munich, Germany., Altomonte J; Department of Internal Medicine II, Rechts der Isar Hospital, Technical University of Munich, 81675 Munich, Germany.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2024 Oct 06; Vol. 16 (19). Date of Electronic Publication: 2024 Oct 06.
DOI: 10.3390/cancers16193405
Abstrakt: Background/objectives: Oncolytic virotherapy is a promising approach in cancer immunotherapy. We have previously described a recombinant hybrid oncolytic virus (OV), VSV-NDV, which has a favorable safety profile and therapeutic immunogenicity, leading to direct oncolysis, abscopal effects, and prolonged survival in syngeneic in vivo tumor models. While OVs are known to mediate systemic anti-tumor immune responses, the detailed characterization of local and systemic immune responses to fusogenic oncolytic virotherapy remains unexplored.
Methods and Results: We analyzed immune cell compartments in the spleen, blood, tumor-draining lymph nodes (TDLNs), and tumors over the course of VSV-NDV therapy in a bilateral syngeneic melanoma mouse model. Our results revealed significant local infiltration and activation of T lymphocytes in tumors and globally in the blood and spleen. Notably, in vivo CD8 + T cell depletion led to complete abrogation of the tumor response, highlighting the crucial role of T cells in promoting the therapeutic effects of oncolytic VSV-NDV. In vitro co-culture experiments enabled the interrogation of human immune cell responses to VSV-NDV-mediated oncolysis. Human peripheral blood mononuclear cells (PBMCs) were efficiently stimulated by exposure to VSV-NDV-infected cancer cells, which recapitulates the in vivo murine findings.
Conclusions: Taken together, these data characterize a broad anti-tumor immune cell response to oncolytic VSV-NDV therapy and suggest that CD8 + T cells play a decisive role in therapeutic outcome, which supports the further development of this chimeric vector as a multimechanistic immunotherapy for solid cancers.
Databáze: MEDLINE
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