Oncolytic Cytomegaloviruses Expressing EGFR-retargeted Fusogenic Glycoprotein Complex and Drug-controllable Interleukin 12

Overview

Journal Cell Rep Med

Publisher Cell Press

Specialties Biology
General Medicine

Date 2024 Dec 18

PMID 39694038

Authors

Haifei Jiang

Rebecca Nace

Coryn Ferguson

Lianwen Zhang

Kah Whye Peng

Stephen J Russell

Affiliations

Soon will be listed here.

Abstract

Cytomegalovirus (CMV) infects a wide range of cell types, including tumor-associated myeloid cells and glioma cells. Clinical observations suggest a potential link between long-term glioblastoma survival and CMV reactivation. We herein present an oncolytic CMV vector, AD169r, which includes a restored pentamer complex gH/gL/pUL128-131 and the removal of UL1-UL20 and UL/b' sequences. The epidermal growth factor receptor (EGFR)-retargeted paramyxoviral glycoprotein H/F complexes are incorporated into AD169r backbone to enhance viral oncolysis. Additionally, a tet-off-controlled single-chain interleukin (IL)-12 is added to boost antitumor immune responses. The engineered oncolytic CMVs expressing EGFR-retargeted H/F complex demonstrate enhanced antitumor efficacy in human glioblastoma xenograft models. In the immunocompetent mouse CT-2A glioblastoma model, an oncolytic murine CMV (mCMV) expressing IL-12 significantly increases the abundance and cytotoxicity of CD4 T cells, CD8 T cells, and CD4CD8 T cells in both treated and untreated tumors. Our findings highlight the potential of the AD169r-derived oncolytic viruses as CMV-based cancer viroimmunotherapy.

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