Retroviral replicating vector-mediated gene therapy achieves long-term control of tumor recurrence and leads to durable anticancer immunity.

ABSTRACT:

Background

Prodrug-activator gene therapy with Toca 511, a tumor-selective retroviral replicating vector (RRV) encoding yeast cytosine deaminase, is being evaluated in recurrent high-grade glioma patients. Nonlytic retroviral infection leads to permanent integration of RRV into the cancer cell genome, converting infected cancer cell and progeny into stable vector producer cells, enabling ongoing transduction and viral persistence within tumors. Cytosine deaminase in infected tumor cells converts the antifungal prodrug 5-fluorocytosine into the anticancer drug 5-fluorouracil, mediating local tumor destruction without significant systemic adverse effects.

Methods

Here we investigated mechanisms underlying the therapeutic efficacy of this approach in orthotopic brain tumor mode

SUBMITTER: Hiraoka K 

PROVIDER: S-EPMC5574670 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature