Molecular therapy oncolytics | VOL. 25
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Redirecting anti-Vaccinia virus Tcell immunity for cancer treatment by AAV-mediated delivery of the VV B8R gene.

Publication Date Jun 16, 2022

Abstract

Immunotherapies, such as immune checkpoint inhibitors (ICIs) and chimeric antigen receptor-T (CAR-T) cells, are only efficient in a small proportion of tumor patients. One of the major reasons for this is the lack of immune cell infiltration and activation in the tumor microenvironment (TME). Recent research reported that abundant bystander CD8+ Tcells targeting viral antigens exist in tumor infiltrates and that virus-specific memory Tcells could be recalled to kill tumor cells. Therefore, virus-specific memory Tcells may be effective candidates for tumor immunotherapy. In this study, we established subcutaneous tumor mice models that were pre-immunized with Vaccinia virus (VV) and confirmed that tumor cells with ectopic expression of the viral B8R protein could be recognized and killed by memory Tcells. To create a therapeutic delivery system, we designed a recombinant adeno-associated virus (rAAV) with a modified tumor-specific promoter and used it to deliver VV B8R to tumor cells. We observed that rAAV gene therapy can retard tumor growth in VV pre-immunized mice. In summary, our study demonstrates that rAAV containing a tumor-specific promoter to restrict VV B8R gene expression to tumor cells is a potential therapeutic agent for cancer treatment in VV pre-immunized or VV-treated mice bearing tumors.

Concepts
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Vaccinia Virus
Chimeric Antigen receptor-T
rAAV Gene Therapy
Virus-specific Tcells
Tumor-specific Promoter
Retard Tumor Growth
Immune Checkpoint Inhibitors
Chimeric Antigen receptor-T Cells
Tumor Infiltrates
Memory Tcells

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