Evaluation of T cells as carriers for systemic measles virotherapy in the presence of antiviral antibodies

Gene therapy progress and prospects cancer: oncolytic viruses

“…Subsequently, the 'carrier cell' approach has been tested by several groups. 13 Using measles viruses, Ong et al 14 showed that virus-infected T cells can protect from low, but not high, concentrations of antimeasles immune serum. However, even in measles-naive mice, only 1-2% of the virus-infected T cells trafficked to the tumor site after systemic delivery.…”

Cell carriers to deliver oncolytic viruses to sites of myeloma tumor growth

“…An assortment of cells have been explored in this regard, including tumor cells, [49][50][51][52] outgrowth endothelial cells, 53 mesenchymal progenitor cells, 54,55 T cells 56,57 and monocytes. 58 There are several criteria that need to be addressed when determining which cell type should be utilized as a carrier for the delivery of a given oncolytic virus: (i) susceptibility to oncolytic virus infection, (ii) protection of the cargo from antibody neutralization, (iii) homing to sites of tumor growth and (iv) transfer of virus progeny to tumor tissue.…”

“…In the case of measles virus, over 90% of American adults have protective titers of antimeasles antibodies. 73 Ong et al 57 recently demonstrated that T cells collected from healthy donors were susceptible to MV infection. In vitro studies illustrated that MV-infected T cells were able to transfer MV infection by heterofusion with myeloma cells.…”

Potential of tumour cells for delivering oncolytic viruses

“…Notably, pre-activation of T cells by phytohaemagglutinin results in increased susceptibility to the measles virus, although infection remains non-productive and viral transfer is achievable only through heterofusion of the vehicle with the target cell. 39 A very recent report describes a potent strategy using cytokine-induced killer cells supporting replication of vaccinia OVs and their transport into tumours upon intravenous administration. 40 Especially attractive candidates would include tumour-infiltrating lymphocytes (TILs).…”

“…47 In other OV/tumour systems, virus delivered by carrier cells was found to avoid seroneutralization partially or totally in actively or passively immunized animals. 6,39 Thus, carrier cell-mediated delivery has a potential to shield input virions against neutralizing antibodies in vivo, but the level of protection appears to depend on the OV/carrier cell pair, the target tumour, the therapeutic protocol (notably treatment repetition, antibody titres). Accordingly, the impact of these parameters should be assessed in immunocompetent animal models where the OV induces a potent neutralizing response.…”