Combination of Mesenchymal Stem Cell-Delivered Oncolytic Virus with Prodrug Activation Increases Efficacy and Safety of Colorectal Cancer Therapy.

ABSTRACT: Although oncolytic viruses are currently being evaluated for cancer treatment in clinical trials, systemic administration is hindered by many factors that prevent them from reaching the tumor cells. When administered systemically, mesenchymal stem cells (MSCs) target tumors, and therefore constitute good cell carriers for oncolytic viruses. MSCs were primed with trichostatin A under hypoxia, which upregulated the expression of CXCR4, a chemokine receptor involved in tumor tropism, and coxsackievirus and adenovirus receptor that plays an important role in adenoviral infection. After priming, MSCs were loaded with conditionally replicative adenovirus that exhibits limited proliferation in cells with a functional p53 pathway and encodes Escherichia coli nitroreductase (NTR) enzymes (CRAdNTR)

SUBMITTER: Ho CT 

PROVIDER: S-EPMC8153168 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature