Oncolytic Virotherapy Development for Melanoma

Creative Biolabs offers oncolytic virotherapy development for melanoma based on our well-established OncoVirapy™ platform which integrates full therapeutics developing process from oncolytic virus construction to function validation both in vitro and in vivo.

Melanoma is a type of skin cancer arising from melanocytes and the incidence is continuing to increase. Although in early stage of the disease, surgical excision remains the standard treatment, metastatic melanoma continues to be a major therapeutic challenge with an increasing number of immunotherapy strategies and targeted drugs. In addition to surgical resection and cytoxic chemotherapy, which have already shown some benefit, such as dacarbazine, an alkylating agent that is FDA-approved for the treatment of metastatic melanoma, new strategies in immuno-oncology have been especially promising over the last several years in terms of the treatment advancement.

Despite that metastatic melanoma has been especially difficult to treat, identification of specific molecular changes will allow for the development of more effective therapy strategies. As a major target for melanoma therapeutics, it shows that BRAF mutations might be involved in 40-60% of melanoma carcinogenesis. BRAF is a proto-oncogene which encodes a kinase as part of the RAS-RAF-MEK-ERK pathway that is able to promote cell growth and proliferation. Nearly half of the metastatic melanomas are reported occurring due to a V600E missense mutation of BRAF. At present, there are some therapeutics approved for the treatment of melanoma, for example, Vemurafenib, Dabrafenib and Trametinib as small molecular inhibitors, and Ipilimumab, Pembrolizumab and Nivolumab as immune checkpoint inhibitors in immunotherapy. Particularly in October 2015, FDA approved the first oncolytic virus therapy called talimogene laherparepvec, a genetically modified live oncolytic herpes virus for the treatment of patients with melanoma lesions in the skin and lymph nodes. Besides, numerous oncolytic viruses are being evaluated in both preclinical and clinical trials for the treatment of melanoma as lots of preclinical tumor models have demonstrated the therapeutic effectiveness of oncolytic viruses. Furthermore, combination approaches are another promising way for the application of oncolytic virotherapy, such as combining oncolytic virus with immune checkpoint inhibitors, BRAF inhibitors and even adoptive T cell therapy.

Oncolytic Virotherapy Development for Melanoma Fig 1. Mechanism of action for T-VEC. (Frederick J. K., 2016)

To promote the application of oncolytic virus as in the treatment of melanoma, Creative Biolabs is now providing full set of oncolytic virotherapy development service. More specifically, after thorough exploitation of melanoma pathogenesis and properties of various type of virus, candidate virus species will be selected and conferred with enhanced antitumor functions by genetic engineering, followed by professionally-designed in vitro and in vivo assays for therapeutic effect validation. In the whole process, not only the antitumor efficacy, but also the safety and other clinical issues will be taken into account. In addition, we are also able to provide oncolytic virotherapy development for other diseases like hepatocellular carcinoma, breast cancer, brain tumors, gastrointestinal cancers, head and neck cancers, mesothelioma, etc.

Reference:

  1. Frederick J. K., (2016). "Molecular Pathways: Mechanism of Action for Talimogene Laherparepvec, a New Oncolytic Virus Immunotherapy." Clin Cancer Res; 22(5)
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