Oncolytic Virotherapy as Emerging Immunotherapeutic Modality: Potential of Parvovirus H-1

Abstract

Human tumors develop multiple strategies to evade recognition and efficient suppression by the immune system. Therefore, a variety of immunotherapeutic strategies have been developed to reactivate and reorganize the human immune system. The recent development of new antibodies against immune check points may help to overcome the immune silencing induced by human tumors. Some of these antibodies have already been approved for treatment of various solid tumor entities. Interestingly, targeting antibodies may be combined with standard chemotherapy or radiation protocols. Furthermore, recent evidence indicates that intratumoral or intravenous injections of replicative oncolytic viruses such as herpes simplex-, pox-, parvo-, or adenoviruses may also reactivate the human immune system. By generating tumor cell lysates in situ, oncolytic viruses overcome cellular tumor resistance mechanisms and induce immunogenic tumor cell death resulting in the recognition of newly released tumor antigens. This is in particular the case of the oncolytic parvovirus H-1 (H-1PV), which is able to kill human tumor cells and stimulate an anti-tumor immune response through increased presentation of tumor-associated antigens, maturation of dendritic cells, and release of pro-inflammatory cytokines. Current research and clinical studies aim to assess the potential of oncolytic virotherapy and its combination with immunotherapeutic agents or conventional treatments to further induce effective antitumoral immune responses.

Treatment of Liver Cancer

“…Oncolytic viruses are designated tumor-selective, multimechanistic antitumor agents, and the commonly used virus classes include adenovirus, parvovirus, herpes simplex virus, poxvirus, paramyxovirus, reovirus, etc. (Russell et al 2012;Moehler et al 2014). The preferential tropism of cancer cells by oncolytic viruses is based on the characteristic impaired antiviral responses and higher permissiveness for virus replication of cancer cells (Russell et al 2012).…”

“…The anticancer effects of oncolytic viruses are multimechanistic, ranging from direct virus-mediated cancer cell killing, pleiotropic cytotoxic immune effector mechanisms, through the specific activities of transgene-encoded proteins (Russell et al 2012). Furthermore, by generating tumor cell lysates in situ, oncolytic viruses may overcome cellular tumor-resistance mechanisms and induce immunogenic tumor cell death resulting in the recognition of newly released tumor antigens (Moehler et al 2014). …”

A good start of immunotherapy in esophageal cancer

“…Many experts believe that oncolytic virus therapy is perhaps another breakthrough in immunotherapy after the success of ICI . Oncolytic viruses selectively replicate in cancer cells and then induce tumor cells lysis.…”

“…Many experts believe that oncolytic virus therapy is perhaps another breakthrough in immunotherapy after the success of ICI. 52,53 Oncolytic viruses selectively replicate in cancer cells and then induce tumor cells lysis. In October 2015, talimogene laherparepvec (or T-Vec), the first oncolytic virus showed clinical benefits and was approved in advanced melanoma patients.…”

Immunotherapy of Esophageal Cancer: Current Status, Many Trials and Innovative Strategies

“…Oncolytic virus therapy is perhaps the next major breakthrough in cancer treatment following the success of CI [31,32]. Oncolytic viruses are defined as genetically engineered or naturally occurring viruses that selectively replicate in and kill cancer cells without harming the normal tissues.…”