Measles virus (MV) is a negative-strand RNA paramyxovirus that is highly fusogenic and induces extensive cytopathic effects of syncytial formation. Intercellular fusion (F) increases bystander killing of tumor cells, and induces immunogenic danger signals which can elicit host-mediated cellular antitumor activity. A successful oncolytic virus is one that selectively propagates and destroys cancerous tissue without causing excessive damage to the normal surrounding tissue. Oncolytic MV is one such virus that exhibits this characteristic and therefore has rapidly emerged as a potentially useful anticancer modality. Derivatives of the Edmonston MV vaccine strain have a remarkable safety record in humans. Promising experimental results in preclinical animal models and evidence of biological activity in early phase trials contribute to the enthusiasm. Genetic modifications have enabled MV to evolve from a vaccine agent to potential anticancer therapy. In particular, alterations of the MV genome have resulted in improved tumor selectivity and delivery, therapeutic potency, and immune system modulation.
Figure 1. Different types of oncolytic measles virus.
So far, recombinant Edmonston strain MV encoding the sodium iodide symporter (MV-NIS) or soluble carcinoembryonic antigen (MV-CEA) is in Phase I/II clinical testing in patients with relapsed or recurrent cancers including multiple myeloma, glioma, ovarian cancer, breast cancer and mesothelioma. For years of experience in immunology and oncology, Creative Biogene has established a comprehensive QVirus™ platform for providing oncolytic virus development service. By virtue of QVirus™ platform, we are able to design, engineering and generate the most efficacious oncolytic measles viral vector and measles viral particles.
A critical component in evaluating oncolytic virus efficacy is the ability to monitor infection and spread. To facilitate its detection, we have developed recombinant MV-GFP and MV-CEA, two MV-Edm derivatives that encode green fluorescent protein (GFP) and carcinoembryonic antigen (CEA), respectively.
Advances in genetic engineering have allowed us to create “armed” viruses which have increased antitumor efficacy. Armed viruses combine the lytic potential of the virus with the therapeutic capacity of a transgene cloned into the viral genome. So far, the most widely studied therapeutic transgene utilized to arm recombinant MV is NIS.
Recombinant MV has successfully been developed to target multiple tumor-associated markers including the epidermal growth factor receptor, epidermal growth factor receptor-vIII, and interleukin-13 receptor α2 found on gliomas, myeloma markers CD38 and CD138, folate receptor α receptor expressed in ovarian cancers, prostate stem cell antigen expressed by prostatic and pancreatic cancers, CD20-positive non-Hodgkin’s lymphoma, and Her-2/neu.
We can also construct recombinant MV which expresses a transgene that stimulates the native antitumor immune response or alters the tumor microenvironment, such as anti-CTLA-4 and PDL-1 antibodies.
Our QVirus™ Platform commits to developing efficacious oncolytic measles virus for the customer and enabling wider applications in oncolytic virotherapy of cancers. Welcome to contact us at email@example.com, if you need help in creating your own modified MVs.
1. Adam S, et al. Advances in the design and development of oncolytic measles viruses. Oncolytic Virotherapy, 2015:109-.
2. Bhattacharjee S , Yadava P K . Measles virus: Background and oncolytic virotherapy. Biochemistry and Biophysics Reports, 2018, 13:58-62.
3. Lapp S, et al. Viral Oncolysis — Can Insights from Measles Be Transferred to Canine Distemper Virus?. Viruses, 2014, 6(6):2340-2375.