Oncolytic virotherapy for urological cancers

Abstract

Oncolytic virotherapy is a cancer treatment in which replication-competent viruses are used that specifically infect, replicate in and lyse malignant tumour cells, while minimizing harm to normal cells. Anecdotal evidence of the effectiveness of this strategy has existed since the late nineteenth century, but advances and innovations in biotechnological methods in the 1980s and 1990s led to a renewed interest in this type of therapy. Multiple clinical trials investigating the use of agents constructed from a wide range of viruses have since been performed, and several of these enrolled patients with urological malignancies. Data from these clinical trials and from preclinical studies revealed a number of challenges to the effectiveness of oncolytic virotherapy that have prompted the development of further sophisticated strategies. Urological cancers have a range of distinctive features, such as specific genetic mutations and cell surface markers, which enable improving both effectiveness and safety of oncolytic virus treatments. The strategies employed in creating advanced oncolytic agents include alteration of the virus tropism, regulating transcription and translation of viral genes, combination with chemotherapy, radiotherapy or gene therapy, arming viruses with factors that stimulate the immune response against tumour cells and delivery technologies to ensure that the viral agent reaches its target tissue.

Bioinspired Artificial Tobacco Mosaic Virus with Combined Oncolytic Properties to Completely Destroy Multidrug‐Resistant Cancer

“…[14] Moreover, challenges still remain in spreading the virus through solid tumors, as high tumor selectivity results in the avoidance noncancerous cell infection, which may restrict viral dissemination in tumor masses that contain large amounts of noncancerous cells, such as stromal cells, endothelial cells, and infiltrating immune cells, preventing the virus from spreading throughout the entire tumor. [14,15] Additionally, virus immunogenicity was not expected. [1a,16] Hence, an artificial virus agent with outstanding composite oncolytic and intercellular dispersal potencies was proposed.…”

Development of Oncolytic Adenoviruses for the Management of Prostate Cancer

“…In both settings, CG7870 was reported to significantly reduce PSA levels. Moreover, CG7870 synergised with other DNA-damaging therapies including radiotherapy or taxane chemotherapy in preclinical models [5,7,48].…”

“…A promising novel class of therapeutics that act through entirely different mechanisms than traditional cytotoxic and targeted drugs is oncolytic viruses. Currently, no oncolytic virus has been approved for treatment of PCa, although numerous phase I-II trials have been completed with promising outcomes and phase III trials are underway [5]. The most promising preclinical and clinical efficacy has been reported for various PCa-selective replicating adenoviral mutants that lyse cancer cells and leave normal cells unharmed and, in addition, resensitise drug-resistant cancer cells to chemotherapeutics [6][7][8].…”

Oncolytic alphavirus SFV-VA7 efficiently eradicates subcutaneous and orthotopic human prostate tumours in mice

“…Oncolytic virotherapy with tumour-specific viruses represents a novel treatment option for such urological malignancies. Indeed, vaccinia-, adeno- and reoviruses have shown promise against prostate cancer in early-phase clinical trials (Delwar et al , 2016). Oncolytic Semliki Forest virus SFV-VA7 has demonstrated significant promise in a variety of murine cancer models, including human melanoma (Vähä-Koskela et al , 2006), osteosarcoma (Ketola et al , 2008), lung carcinoma (Määttä et al , 2008), glioma (Heikkilä et al , 2010) and syngeneic colorectal carcinoma (Ruotsalainen et al , 2015), but its potential against prostate cancer has thus far remained unexplored.…”