MMP-loaded Oncolytic Vaccinia Virus
Introduction of MMP-based VACV
As a promising alternative to classical tumor treatment methods such as surgery, chemotherapy, and radiotherapy, oncolytic vaccinia virus (VACV) presents great potentials for tumor treatment. VACV can only replicate in the cytoplasm and contains a large genome well for insertion of up to 25 kb. The establishment of recombinant VACVs (rVACVs) can enhance therapeutic efficacy and allow the use of imaging techniques. Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases, which are usually expressed as inactive zymogens. In the activated state, MMPs are important for the degradation of extracellular matrix (ECM) components, including laminin, collagen, elastin, and fibrillin. The cleavage of ECM proteins results in the shedding of ECM-bound growth factors and multiple functions.
It has been reported that ECM is the hindrance for viral cell-to-cell spreading and then decrease the oncolytic effect. Some studies showed that the insertion of the relaxin gene in adenoviruses leads to degradation of ECM components and further viral spreading improvement in the tumor microenvironment. Compared with the wild-type VACVs, the rVACVs present higher viral titers and accelerated tumor regression.
Fig.1 Expression of functional MMP-9 by GLV-1h255-infected tumor cells. (Schäfer, 2013)
MMP-based VACV in Cancer Treatment
Prostate cancer (PCa) is common cancer in the US and the death is always caused by the formation of metastases.
- The GLV-1h68 has been successfully used in a series of cancers, including pancreatic tumors, breast cancer, and squamous cell carcinoma.
- GLV-1h255 is the oncolytic vaccinia virus containing the MMP-9 gene. The therapeutic efficacy can be evaluated by monitoring tumor growth kinetics and intra-tumoral virus titers. Using the animal model with PC-3 tumors, the treatment of GLV-1h255 led to a significant over-expression of MMP-9 and a marked decrease of collagen IV content.
- In addition, intra-tumoral viral dissemination has been promoted and also results in accelerated tumor regression. The studies also showed that both GLV-1h68 and GLV-1h255 can reduce the size of lumbar and renal lymph code metastases, which means that the expression of MMP-9 enhances virotherapy of the primary tumor and also sustains the rVACV-metastasis reducing effect.
Fig.2 Replication kinetics of GLV-1h68 and GLV-1h255 in PC-3 cells. (Schäfer, 2013)
Creative Biolabs has been a long-term expert in the field of the oncolytic virus. Now we provide a one-stop oncolytic vaccinia virus enhancement service for our clients all over the world.
Reference
- Schäfer, S.; et al. Vaccinia virus-mediated intra-tumoral expression of matrix metalloproteinase 9 enhances oncolysis of PC-3 xenograft tumors. BMC cancer. 2012, 12(1): 1-9.