Abstract
Oncolytic viruses (OVs) are an emerging class of therapeutics which combine multiple mechanisms of action, including direct cancer cell-killing, immunotherapy and gene therapy. A growing number of clinical trials have indicated that OVs have an excellent safety profile and provide some degree of efficacy, but to date only a single OV drug, HSV-1 talimogene laherparepvec (T-Vec), has achieved marketing approval in the US and Europe. An important issue to consider in order to accelerate the clinical advancement of OV agents is the development of an effective delivery system. Currently, the most commonly employed OV delivery route is intratumoral; however, to target metastatic diseases and tumors that cannot be directly accessed, it is of great interest to develop effective approaches for the systemic delivery of OVs, such as the use of carrier cells. In general, the ideal carrier cell should have a tropism towards the tumor microenvironment (TME), and it must be susceptible to OV infection but remain viable long enough to allow migration and finally release of the OV within the tumor bed. Mesenchymal stem cells (MSCs) have been heavily investigated as carrier cells due to their inherent tumor tropism, in spite of some disadvantages in biodistribution. This review focuses on the other promising candidate carrier cells under development and discusses their interaction with specific OVs and future research lines.
Highlights
The last century has witnessed substantial progress in the so-called “war on cancer” [1]
A major hurdle to the clinical translation and market entry of oncolytic virotherapy is the lack of simple, clinician- and patient-friendly administration methods that are effective in the tumor-specific delivery of viral vectors
While a lot of effort has been focused on the generation of elaborate, genetically engineered Oncolytic viruses (OVs) with enhanced selectivity and/or therapeutic gene expression, it is difficult to imagine that, in real-world clinical practice, large numbers of cancer patients can be treated by intratumoral injection of therapeutic viruses
Summary
The last century has witnessed substantial progress in the so-called “war on cancer” [1]. The problem of targeting metastases was addressed by relying on the “in situ vaccine” effect [31] According to this hypothesis, the lytic effect of the virus is limited to the primary tumor in which it is injected, but the immune response against tumor-associated antigens (TAAs) will be of 11 effective against the uninjected masses. MSCs were shown to have pharmacokinetic challenges, accumulating mainly in the lungs of experimental animals following intravenous injection, probably due to their dimensions These problems resulted in some research groups trying to use MSCs for intratumoral delivery, which can make sense in some particular instances but mostly seems to contradict the rationale for the use of carrier cells
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