Abstract
The field of therapeutic stem cell and oncolytic virotherapy for cancer treatment has rapidly expanded over the past decade. Oncolytic viruses constitute a promising new class of anticancer agent because of their ability to selectively infect and destroy tumor cells. Engineering of viruses to express anticancer genes and specific cancer targeting molecules has led to the use of these systems as a novel platform of metastatic cancer therapy. In addition, stem cells have a cancer specific migratory capacity, which is available for metastatic cancer targeting. Prodrug activating enzyme or anticancer cytokine expressing stem cells successfully inhibited the proliferation of cancer cells. Preclinical models have clearly demonstrated anticancer activity of these two platforms against a number of different cancer types and metastatic cancer. Several systems using therapeutic stem cells or oncolytic virus have entered clinical trials, and promising results have led to late stage clinical development. Consequently, metastatic cancer therapies using stem cells and oncolytic viruses are extremely promising. The following review will focus on the metastatic cancer targeting mechanism of therapeutic stem cells and oncolytic viruses, and potential challenges ahead for advancing the field.
Highlights
Cancer metastasis, which is a multiple process in which malignant cells spread from the primary site to colonize distant organs, is one of the greatest challenges in cancer treatment
Overexpression of the CXCR4 using gene transfection of human umbilical cord blood derived MSCs increased the migratory capacity of MSCs toward gliomas [15]. These results show the possibility to further increase migration capacity toward metastatic cancer via stem cell engineering
Insertion of liver specific microRNA binding sites in the 3’ untranslated region (UTR) of the gene encoding E1A of an oncolytic adenovirus decreased its toxicity without sacrificing tumor killing activity in a model of pancreatic cancer metastasis to the liver [58]
Summary
Cancer metastasis, which is a multiple process in which malignant cells spread from the primary site to colonize distant organs, is one of the greatest challenges in cancer treatment. We will discuss recent strategies for the treatment of metastatic cancer based on stem cells and oncolytic viruses. Stem cells can be modified to stably express various anticancer agents including cytokines and prodrug activating enzymes for induction of cancer apoptosis and removal of specific tumors.
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