Mesenchymal Stromal Cells Protect Combined Oncolytic and Helper-Dependent Adenoviruses From Humoral Immunity

Authors

Ada Irmak Özcan
Arianexys Aquino Lόpez
Alexandra N Wolff
Audrey Ma
Amanda Rosewell Shaw
Masataka Suzuki
Malcolm K Brenner
Mary K McKenna

Publication Date

9-12-2024

Journal

Molecular Therapy Methods & Clinical Development

DOI

10.1016/j.omtm.2024.101279

PMID

38993326

PMCID

PMC11238183

PubMedCentral® Posted Date

6-6-2024

PubMedCentral® Full Text Version

Post-Print

Published Open-Access

yes

Keywords

mesenchymal stromal cells, oncolytic adenovirus, helper-dependent adenovirus, three-dimensional tumor spheroids, solid tumors

Abstract

Systemic delivery of oncolytic and immunomodulatory adenoviruses may be required for optimal effects on human malignancies. Mesenchymal stromal cells (MSCs) can serve as delivery systems for cancer therapeutics due to their ability to transport and shield these agents while homing to tumors. We now use MSCs to deliver a clinically validated binary oncolytic and helper-dependent adenovirus combination (CAdVEC) to tumor cells. We show successful oncolysis and helper-dependent virus function in tumor cells even in the presence of plasma from adenovirus-seropositive donors. In both two- and three-dimensional cultures, CAdVEC function is eliminated even at high dilutions of seropositive plasma but is well sustained when CAdVEC is delivered by MSCs. These results provide a robust

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