Clinical development directions in oncolytic viral therapy

Abstract

Oncolytic virotherapy is an emerging experimental treatment platform for cancer therapy. Oncolytic viruses are replicativecompetent viruses that are engineered to replicate selectively in cancer cells with specified oncogenic phenotypes. Multiple DNA and RNA viruses have been clinically tested in a variety of tumors. This review will provide a brief description of these novel anticancer biologics and will summarize the results of clinical investigation. To date oncolytic virotherapy has shown to be safe, and has generated clinical responses in tumors that are resistant to chemotherapy or radiotherapy. The major challenge for researchers is to maximize the efficacy of these viral therapeutics, and to establish stable systemic delivery mechanisms.

Ionizing radiation enhances dl922–947-mediated cell death of anaplastic thyroid carcinoma cells

“…OVs represent a promising approach as anti-cancer therapeutics; however preclinical and clinical studies have demonstrated limited efficacy of OVs alone, prompting effort to combine them with other anti-cancer agents to improve their antitumor effects (Eager & Nemunaitis 2011. We have previously demonstrated that the oncolytic adenoviruses dl1520 and dl922-947 are active against ATC in vitro and in vivo (Libertini et al 2007(Libertini et al , 2008.…”

“…With respect to classical anti-cancer drugs, OVs present several advantages: tumor-selective replication with amplification of the input dose, stimulation of anti-tumoral immune responses, and relatively few mild side effects when administered to human patients. Also, the development of cross-resistance is unlikely because their mechanism of action is independent of conventional anti-cancer therapeutics (Eager & Nemunaitis 2011. A number of OVs, such as the vaccinia virus GLV-1h68 (Lin et al 2008b) and the oncolytic attenuated herpes virus G207 (Lin et al 2008a), have shown promising effects against ATC cells in preclinical studies.…”

Adenovirus: The First EffectiveIn VivoGene Delivery Vector

“…antiadenovirus immunity is vigorous, many groups have made it even more so by generating replication-competent adenoviruses as therapeutic strategies to treat cancer, that is, to enlist the antiadenovirus immunity in killing cancer cells (Short and Curiel, 2009;Eager and Nemunaitis, 2011;Alemany, 2012;Cerullo et al, 2012;Russell et al, 2012;Choi and Yun, 2013). Third, we and others have leveraged the potent immunity against the adenovirus to create vaccines against the transgene (Krause and Worgall, 2011) or by inserting the antigen in the capsid (Lasaro and Ertl, 2009;Thacker et al, 2009;Matthews, 2011).…”

Advance in herpes simplex viruses for cancer therapy

“…One or more  sequences with 400 base pair (bp) join the L and S segments. Gene-modified HSV includes inactivation of ICP6 gene and deletion of -34.5 [12]. ICP6 encodes the large subunit of ribonucleotide reductase, which is essential for viral DNA replication.…”