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.
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.
An oncolytic vaccinia virus has been successfully used in a variety of cancers, including pancreatic tumors, breast cancer, and squamous cell carcinoma. Another modified vaccinia virus containing the MMP-9 gene has shown therapeutic efficacy that can be evaluated by monitoring tumor growth kinetics and intra-tumoral virus titers. In an animal model with PC-3 tumors, treatment with this virus led to significant over-expression of MMP-9 and a marked decrease in collagen IV content. Additionally, intra-tumoral viral dissemination was promoted, resulting in accelerated tumor regression. Studies also demonstrated that this approach can reduce the size of lumbar and renal lymph node metastases, indicating that MMP-9 expression enhances virotherapy of the primary tumor and supports the metastasis-reducing effect of the virus.
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.