Oncolytic viruses for the therapy of brain tumors and other solid malignancies a review

Abstract

In spite of significant advances in the understanding of molecular processes in tumor biology that have led to the development of oncologic therapeutic strategies, the prognosis for several types of tumors (such as brain, pancreas, or hepatic malignancies) remains dismal. Without question, a strong need exists for continued investigations in new agents and new therapeutic regimens. The realization that several genes used by viruses in their lytic life cycle interact and/or complement the function of genes employed by cells in cellular events linked to cell cycle progression, apoptosis, and/or metabolism immediately suggests the development of treatment strategies wherein viral mutants could be employed as selective anticancer agents. Such viruses (designated as oncolytic viruses) can selectively grow in tumor cells, produce viral progeny in those cells, lyse them and release this progeny that can then infect additional cells in the tumor mass. A theoretical advantage of oncolytic viruses (OV) is that their numbers should augment within the tumor mass, a property that is lacking with drugs or radiation treatments. Additionally, Ovs' mode of tumor killing differs from standard anticancer agents, providing the possibility for synergistic interactions in multimodal tumor therapies. In this review, we will describe the development of OVs and briefly review the life cycle of their wild-type (wt) counterparts. We will also summarize published results from OV clinical trials and attempt to provide a perspective on research in this area.

Real-time imaging of TRAIL-induced apoptosis of glioma tumors in vivo

“…Our results show that both soluble TRAIL and membrane-bound TRAIL delivered to the glioma cells by HSV-amplicon vectors have a similar effect on cell killing. Recombinant HSV vectors, for example, deleted for ribonucleotide reductase, (hrR3) have been shown previously to replicate preferentially in and kill tumor cells (Boviatsis et al, 1994;Fulci and Chiocca, 2003). The safety of oncolytic viral therapy depends on the selectivity of viral replication in dividing cell as compared to postmitotic brain cells.…”

Deciphering the Multifaceted Relationship between Oncolytic Viruses and Natural Killer Cells

“…In fact, recruitment of infiltrating monocytic cells has been shown to coincide with clearance of over 80% of HSV-derived oncolytic viral particles [38, 39]. Increased intra-tumoral presence of macrophage/microglia cells has also been reported in human patients treated with adenovirus [40, 41] or HSV-1-derived OV [42] indicating the global significance of macrophages in OV therapy.…”

Anti-tumor Synergistic Effect of a Dual Cancer-Specific Recombinant Adenovirus and Paclitaxel on Breast Cancer

“…Oncolytic viruses (OVs) are emerging as important agents in cancer treatment as they offer the attractive therapeutic combination of tumor-selective cell lysis and by acting as potential in situ tumor vaccines (3)(4)(5)(6)(7)(8). Early clinical trials of OVs showed encouraging safety profiles, even at high doses, and with some promising responses, such as the evidence of intratumor viral replication and efficient killing of tumors (9)(10)(11).…”