Cancer and viruses: A double-edged sword (original) (raw)

Oncolytic Viruses—Interaction of Virus and Tumor Cells in the Battle to Eliminate Cancer

Frontiers in Oncology

Oncolytic viruses (OVs) are an emerging treatment option for many cancer types and have recently been the focus of extensive research aiming to develop their therapeutic potential. The ultimate aim is to design a virus which can effectively replicate within the host, specifically target and lyse tumor cells and induce robust, long lasting tumor-specific immunity. There are a number of viruses which are either naturally tumor-selective or can be modified to specifically target and eliminate tumor cells. This means they are able to infect only tumor cells and healthy tissue remains unharmed. This specificity is imperative in order to reduce the side effects of oncolytic virotherapy. These viruses can also be modified by various methods including insertion and deletion of specific genes with the aim of improving their efficacy and safety profiles. In this review, we have provided an overview of the various virus species currently being investigated for their oncolytic potential and the positive and negative effects of a multitude of modifications used to increase their infectivity, anti-tumor immunity, and treatment safety, in particular focusing on the interaction of tumor cells and OVs.

Future directions: oncolytic viruses

Clinical lung cancer, 2004

Oncolytic viruses offer a promising new modality for cancer treatment. The strategy of this therapy is to develop viruses capable of selectively infecting and replicating in malignant tumor cells. Oncolytic viruses can spread and destroy malignant tumors without deleterious effects in normal tissues. These viruses are genetically engineered based on both the biology of replicating viruses and the major genetic defects in human cancer cells, so that they can replicate in cancer cells but not in normal cells. The key to the development of such viruses is the identification of viral genes, the deletion or modification of which enables tumor-specific cell destruction. Several clinical trials have demonstrated the safety of oncolytic viruses as cancer therapy and have also shown some encouraging results. Much evidence suggests that oncolytic viral therapy works in synergy with standard cancer therapies. In this review, we will focus on the oncolytic viruses that may be beneficial to pati...

Human oncogenic viruses and cancer

The role of viral infection in cancer was established towards the beginning of 20th century. The study of tumour viruses, their oncogenes and different mechanisms employed by these viruses to subvert the growth-suppressive and pro-apoptotic functions of host tumour suppressor genes has laid the foundation of cancer biology. The human tumour viruses induce malignancies after a prolonged latency and in conjunction with other environmental and host factors. The eight known human tumour viruses contribute to nearly 10–15% of the cancers worldwide. Advancements in research on virus-related cancers offer a plethora of opportunities to fight cancer by preventing viral spread through vaccination and use of antivirals. Besides, recent developments on viral oncogenic mechanisms should allow development of novel and targeted approaches for control and treatment of virus-associated human cancers.

Oncolytic Viruses -A New Era for Cancer Therapy

Journal of Life Science, 2019

Oncolytic viruses have primarily the unique advantage in the fact that they can only infect and destroy cancer cells. Secondary, oncolytic viruses induce the activation of specific adaptive immunity which targets tumor-associated antigens that were hidden during the initial cancer progression. In 2015, one genetically modified oncolytic virus, talimogene laherparepvec (T-VEC), was approved by the American Food and Drug Administration (FDA) for the treatment of melanoma. Currently, various oncolytic viruses are being investigated in clinical trials as monotherapy or in combination with preexistent cancer therapies like immunotherapy, radiotherapy or chemotherapy. The efficacy of oncolytic virotherapy relies on the balance between the induced anti-tumor immunity and the anti-viral response. Despite the revolutionary outcome, the development of oncolytic viruses for the treatment of cancer faces a number of obstacles such as delivery method, neutralizing antibodies and induction of antiviral immunity due to the complexity, variability and reactivity of tumors. Intratumoral administration has been successful reducing considerably solid tumors with no notable side effects unfortunately some tumors are not accessible (brain) and require a systemic administration of the oncolytic viruses.

Molecular Mechanisms Associated with Virus-induced Oncogenesis and Oncolysis

Cancer Research Journal

Cancer is a leading cause of human deaths worldwide. Besides inherited genetic disorders, a diverse range of physical, chemical and biological agents may induce cancer. About 15-20% of cancers are known to be originated due to pathogens. Viruses are considered to be the second (after smoking) most important risk factor in inducing human cancer. Viruses may either harbour a copy of oncogene or have an ability to alter the expression of cellular copy of the oncogenes. Both RNA and DNA viruses are can induce oncogenesis. Most of the DNA tumour viruses either integrate their genome (complete or part of it) into the host genome or express early genes that are required for early event of virus replication. These early genes are responsible for oncogenic transformation of host cells. Based upon the mechanism involved, oncogenic RNA viruses are divided into two groups-transforming and non-transforming RNA viruses. Transforming RNA viruses carry viral oncogenes that are homologous to the host oncogene, their expression in infected cells results in oncogenic transformation of the cell. Non-transforming RNA viruses induce oncogenesis similar to the DNA viruses. Contrary, oncolytic viruses selectively replicate in cancerous cells and induce cell death without any damage to the normal tissues. Typically, oncolytic viruses are nonpathogenic to humans that can naturally replicate in cancer cells by exploiting oncogenic cell signalling pathways. Pathogenic viruses can also be genetically manipulated which allow them to replicate in cancerous but not in normal cells. This review review describes the molecular mechanisms associated with virus induced oncogenesis and oncolysis.

Oncolytic viruses as therapeutic cancer vaccines

Molecular Cancer, 2013

Oncolytic viruses (OVs) are tumor-selective, multi-mechanistic antitumor agents. They kill infected cancer and associated endothelial cells via direct oncolysis, and uninfected cells via tumor vasculature targeting and bystander effect. Multimodal immunogenic cell death (ICD) together with autophagy often induced by OVs not only presents potent danger signals to dendritic cells but also efficiently cross-present tumor-associated antigens from cancer cells to dendritic cells to T cells to induce adaptive antitumor immunity. With this favorable immune backdrop, genetic engineering of OVs and rational combinations further potentiate OVs as cancer vaccines. OVs armed with GM-CSF (such as T-VEC and Pexa-Vec) or other immunostimulatory genes, induce potent anti-tumor immunity in both animal models and human patients. Combination with other immunotherapy regimens improve overall therapeutic efficacy. Coadministration with a HDAC inhibitor inhibits innate immunity transiently to promote inf...

Oncolytic Viruses for Cancer Therapy: Overcoming the Obstacles

Viruses, 2010

Targeted therapy of cancer using oncolytic viruses has generated much interest over the past few years in the light of the limited efficacy and side effects of standard cancer therapeutics for advanced disease. In 2006, the world witnessed the first government-approved oncolytic virus for the treatment of head and neck cancer. It has been known for many years that viruses have the ability to replicate in and lyse cancer cells. Although encouraging results have been demonstrated in vitro and in animal models, most oncolytic viruses have failed to impress in the clinical setting. The explanation is multifactorial, determined by the complex interactions between the tumor and its microenvironment, the virus, and the host immune response. This review focuses on discussion of the obstacles that oncolytic virotherapy faces and recent advances made to overcome them, with particular reference to adenoviruses.

Oncolytic Viruses as Anticancer Vaccines

Frontiers in Oncology, 2014

Oncolytic virotherapy has shown impressive results in preclinical studies and first promising therapeutic outcomes in clinical trials as well. Since viruses are known for a long time as excellent vaccination agents, oncolytic viruses are now designed as novel anticancer agents combining the aspect of lysis-dependent cytoreductive activity with concomitant induction of antitumoral immune responses. Antitumoral immune activation by oncolytic virus infection of tumor tissue comprises both, immediate effects of innate immunity and also adaptive responses for long lasting antitumoral activity, which is regarded as the most prominent challenge in clinical oncology. To date, the complex effects of a viral tumor infection on the tumor microenvironment and the consequences for the tumor-infiltrating immune cell compartment are poorly understood. However, there is more and more evidence that a tumor infection by an oncolytic virus opens up a number of options for further immunomodulating interventions such as systemic chemotherapy, generic immunostimulating strategies, dendritic cell-based vaccines, and antigenic libraries to further support clinical efficacy of oncolytic virotherapy.

Trial Watch:: Oncolytic viruses for cancer therapy

Oncoimmunology, 2014

Oncolytic viruses are natural or genetically modified viral species that selectively infect and kill neoplastic cells. Such an innate or exogenously conferred specificity has generated considerable interest around the possibility to employ oncolytic viruses as highly targeted agents that would mediate cancer cell-autonomous anticancer effects. Accumulating evidence, however, suggests that the therapeutic potential of oncolytic virotherapy is not a simple consequence of the cytopathic effect, but strongly relies on the induction of an endogenous immune response against transformed cells. In line with this notion, superior anticancer effects are being observed when oncolytic viruses are engineered to express (or co-administered with) immunostimulatory molecules. Although multiple studies have shown that oncolytic viruses are well tolerated by cancer patients, the full-blown therapeutic potential of oncolytic virotherapy, especially when implemented in the absence of immunostimulatory ...