Oncolytic Virotherapy Development for Lung Cancer
Lung cancer is the leading cause of cancer mortality in both men and women, with an overall 5-year survival of less than 15%, due to late-stage diagnoses and a lack of efficacious therapies. Currently, surgery, radiotherapy, and chemotherapy continue to be the standard first-line treatment options for lung cancer. Despite initial positive responses to therapy, most of the patients develop resistance to chemotherapy, finally resulting in the relapse of the disease. Therefore, novel treatment strategies with the completely new mechanism of therapeutic activity are required for lung cancer to enhance patient survival.
Oncolytic Viruses (OVs) that are self-replicating biotherapeutics, enable to eliminate tumors through both oncolysis and induction of specific tumor-targeted immune responses in the host. Due to the capacity of inducing tumor antigen release and inflammatory cytokine production, viral oncolysis is able to adapt the tumor microenvironment to one that promotes tumor antigen uptake and thus the maturation of antigen presenting cells such as dendritic cells. Based on Creative Biolabs' oncolytic virus development platform OncoVirapy™, coupled with our enhancing understanding of tumor oncology in lung cancers, our scientists are capable of developing specific oncolytic virotherapy strategy, as well as providing OV construction and validation services to customers.
Fig. 1 Mechanisms of tumour destruction via oncolytic virotherapy. (Marchini, A., 2016)
Oncolytic Viruses (OVs) for Lung Cancer
OVs stand for a promising therapeutic platform for the treatment of human cancer with special attributes compared with typical therapeutic modalities. OVs can selectively infect and lyse tumor cells whereafter the released progeny virions reinfect neighboring tumor cells and enter the bloodstream to infect metastasized tumor cells, while ideally leaving normal cells unharmed. Nowadays, adenoviruses are extensively applied as viral agents in cancer therapy, since they have an inherent potential to kill the cells that sustain their replication, and they are considered to be safe and have been applied in a variety of clinical settings. H101 is a conditionally replicative adenovirus that is developed by both E1B and E3 gene deletion and selectively infects and kills tumor cells via viral oncolysis. In China, H101 has been clinically approved for the treatment of a number of malignancies. A study has explored the CAR expression of lung cancer cells and cytopathologic effects of H101 infection on cancer cells in vitro, which also exhibit that H101 virus suppresses lung cancer xenografts growth in vivo.
Combination Therapy of Oncolytic Viruses (OVs)
OVs can also be used as combination therapy with other treatment strategies. For example, NV1066, a multi-mutated replication-competent oncolytic HSV-1 virus, contains a gene for the marker proteins enhanced green fluorescent protein (EGFP). This HSV-1 virus was studied in the research of combination use of radiation therapy with oncolytic HSV therapy. This study exhibited the cellular basis for the clinical investigation of combined use of radiation therapy with oncolytic HSV therapy in the treatment of lung cancer to achieve synergistic efficacy while minimizing dosage and toxicity. At present, HSV mediated oncolysis and gene therapy have raised as promising treatment modalities against cancer. Oncolysis results from the replicative life cycle of the virus, which lyses infected tumor cells and releases viral progeny for further infection and killing of neighboring cancer cells.
With the need for novel therapeutic strategies in lung cancers, oncolytic virus continues to hold promise as an effective treatment. Creative Biolabs will keep striving to exploit this novel approach to cross the remained barriers and to develop more efficient oncolytic virotherapy strategies for our customers.
Reference:
- Adusumilli, P. S., (2005). "Radiation therapy potentiates effective oncolytic viral therapy in the treatment of lung cancer." The Annals of thoracic surgery, 80(2), 409-417.
- Marchini, A., (2016). "Overcoming barriers in oncolytic virotherapy with HDAC inhibitors and immune checkpoint blockade." Viruses, 8(1), 9.