Oncolytic viruses have become serious contenders in cancer treatment. They preferentially infect and lyse cancer cells whilst leaving normal tissue unharmed. Measles virus (MV) is potentially oncotropic in nature and holds oncolytic properties by syncytia formation. With years of experience in immunology and oncology, Creative Biolabs provides a one-stop solution for oncolytic measles virus construction and engineering. Our brilliant scientists can manipulate the genome of measles virus to obtain novel and effective recombinant oncolytic MV. The oncolytic viruses can be manipulated to alter the capsid to reduce pathogenicity and immunogenicity, to secrete antibody to boost the anti-tumor immune response, to express cytokine/chemokine to attract immune cells migration to the tumor site, and even to be loaded with immune checkpoint inhibitors.
MV is a member of the genus Morbillivirus under the family Paramyxoviridae of the Mononegavirales. It is an enveloped single-stranded negative-sense RNA virus with a 16 kb long genome comprising six genes that encode eight viral proteins: the nucleoprotein (N), phosphoprotein (P), matrix (M), fusion (F), hemagglutinin (H) and large (L) protein, as well as the two accessory non-structural proteins C and V which are encoded by the P-cistron. The viral genome is encapsidated by N, P and L proteins forming the ribonucleoprotein complex (RNP), which is surrounded by M protein. V and C are primarily implicated in the prevention of type 1 interferon (IFN)-induced immune responses. H and F proteins mediate virus attachment and fusion, respectively.
Fig.1 A diagrammatic representation of the measles virus structure. (Aref, 2016)
The H glycoprotein naturally interacts with the three known MV receptors: CD150 or signal lymphocyte-activation molecule (SLAM), CD46, and nectin-4, also known as Poliovirus receptor-related 4 (PVRL4).
MV virotherapy is mainly based on the tumor-selective oncolytic properties of the attenuated MV vaccine strains derived from the MV-Edm vaccine lineage. MV-Edm derivatives preferentially enter cells via MV CD46 receptor and show considerable genetic stability and less pathogenicity. MV-Edm vectors and MV-Edm-based oncolytic therapeutics have now been investigated in a wide range of solid and hematologic malignancies.
Reverse genetic system opened the door for the generation of recombinant MVs encoding additional transcription units (reporter gene, cytokine/chemokine, suicide gene) as well as the modification of viral structural and nonstructural protein to modulate virus biology.
Fig.2 Summary of modifications introduced into MV-Edm through genetic engineering. (Hutzen, 2015)
The genetic modifications of MV are summarized in the following table.
Table.1 Summary of genetically engineered MV. (Aref, 2016)
The clinical application of MV’s properties in developing a virotherapeutic vector system is being highlighted by scientific and medical institutions. By using a clonal reverse genetics system, we can generate diversified recombinant viruses to meet different demands from global customers. Our versatile OncoVirapy™ platform allows producing new viruses expressing very large amounts of additional genetic material. We provide a comprehensive range of services covering the whole pipeline of oncolytic MV construction.
Fig.3 Workflow of oncolytic MV construction at Creative Biolabs.
In addition to recombinant MV construction, Creative Biolabs also offers customized oncolytic MV engineering services to promote oncolytic efficiency and safety. Besides, the proof-of-concept validation assay (in vitro and in vivo validation study) for the oncolytic virus is also provided.
Please feel free to contact us for a quote and further discussion with our scientists.