Oncolytic Vaccinia Virus
Oncolytic vaccinia virus (VACV) has emerged as an attractive therapeutic candidate for cancer treatment due to its inherent ability to specifically target and lyse tumor cells as well as induce antitumor effects by multiple action mechanisms. With years of experience in immunology and oncology, Creative Biolabs has established a comprehensive platform - OncoVirapy™ for providing oncolytic VACV design, engineering and construction services.
Brief Introduction of Oncolytic VACV
Vaccinia virus (VACV or VV) is a large, complex, enveloped DNA virus which belongs to the poxvirus family. It has a linear, double-stranded DNA genome approximately 190 kb in length, encoding approximately 250 genes. VACV is a naturally oncolytic virus which was found to have a natural tropism for tumor cells due to its sensitivity to type I interferon. The strains Lister, Wyeth, and Western Reserve are the most used in OV research, both of which can incorporate large amounts of foreign DNA without reducing their replication efficiency. Moreover, VACV entry does not have a specific receptor which makes it a potential candidate for the treatment of all tumor types. VACV has many inherent characteristics that make it an ideal choice for oncolytic virotherapy, including the ability to infect a wide range of tumor types with efficient infection and gene expression, a large amount of foreign DNA to be incorporated and potent lytic activity, selectively target and infect cancer cells in vivo.
Table.1 Vaccinia virus strains. (Guse, 2011)
Recombinant Oncolytic VACV
Recent advances in DNA recombinant technology enabling the rational manipulation of the VACV backbone, coupled with the ever increasing knowledge gains in the fields of molecular virology and cancer cell biology have aided the development of safe and efficacious tumor-targeted oncolytic VACVs. Four major advances have recently been made to recombinant VACVs to improve their utility as OVs.
- Cancer selective oncolytic VACV
Although VACV has remarkable natural tumor tropism, scientists have tried to engineer VACV with more tumor specificity. Different strategies have been pursued based on genetic engineering of the VV genome to increase cancer tissue specific replication.
Table.2 Common genes of VACV genetic engineering to enhance tumor specificity.
- Modification of VACV viral vectors for improved immunogenicity
The key viral genes to be manipulated are those whose products interact with the host leading to altered immunogenicity (innate and adaptive immunity). These represent cogent targets for genetic manipulation to enhance viral vector immunogenicity.
Table.3 Common genes of VACV to modulate immune responses. (Guo, 2019)
- Armed oncolytic VACVs
Oncolytic VACVs can amplify in tumor tissue and express high local concentrations of transgenes, thus, engineering oncolytic VVs to express therapeutic proteins is a good way to potentiate antitumor efficacy. Researchers have armed VACV viral vectors with genes encoding specific tumor-associated antigens (TAAs), suicide gene, neoantigens and/or immunostimulatory molecules.
Table.4 Examples of oncolytic VACV used in preclinical studies. (Guo, 2019)
Featured Services and Construction Workflow
We provide a comprehensive range of VACV services based on our advanced OncoVirapy™ platform.
- GOI cloning (e.g., antibody, bispecific antibody, cytokine, chemokine, shRNA or gRNA) and confirmation through restriction mapping and sequencing verification
- Functional validation of transgenes
- Expression cassette design with the most appropriate promoter to guarantee the high-level expression
- Viral genes engineering (single gene or different genes combination)
- Different construction strategies (homologous recombination, BAC system, etc.)
- VACV amplification, purification, titering services
- VACV whole genome sequencing (WGS) service
Fig.2 Workflow of oncolytic VACV construction at Creative Biolabs.
Oncolytic VACV has been shown to be a safe and promising anti-cancer agent. Nowadays as a tool for delivering genes into cancer cells, the vaccinia virus shows promising clinical efficacy not only in medicine laboratory but also in Phase I and Phase II trials. Moreover, VACVs are being investigated in combination with various other anti-cancer strategies, including chemo-, radio-, and immunotherapies as well as other oncolytic VACVs. The OncoVirapy™ platform in the Creative Biolabs provides a one-stop solution to oncolytic virus construction and oncolytic virus engineering. We also provide customized oncolytic vaccinia virus and proof-of-concept in vitro and in vivo validation study for the oncolytic VACVs.
References
- Guo, Z. S.; et al. Vaccinia virus-mediated cancer immunotherapy: cancer vaccines and oncolytics. Journal for immunotherapy of cancer. 2019, 7(1): 6.
- Guse, K.; et al. Oncolytic vaccinia virus for the treatment of cancer. Expert opinion on biological therapy. 2011, 11(5): 595-608.