Oncolytic virus is a group of viruses that specifically infect and lyze tumor cells instead of healthy cells. Creative Biolabs provides a broad range of oncolytic virus engineering scope including but not limited to Adenovirus, Herpes Simplex Virus, Measles Virus, Vaccinia Virus, Vescilar Stomatitis Virus, and Adeno-Associated Virus.
Adenovirus has been explored and engineered extensively as an oncolytic virus and viral vector for gene therapy to reduce viral virulence and increase efficacy and specificity. E1A gene in adenovirus is responsible for viral replication in tumor cells and needs to be attenuated for oncolytic purpose. Coated protein modification is to increase target specificity of adenovirus to tumor cells, and thus alters viral tropism. Adenovirus can also be modified through transcriptional targeting, such as placing E1A and E1B gene under control of promoter of cyclooxygenase-2 enzyme (highly expressed in a range of cancers), or through post-transcriptional modification, such as targeting of cancer specific miRNA.
HSV is another group of viruses developed for cancer immunotherapy. The melanoma oncolytic HSV is the first-in-class FDA-approved genetically modified oncolytic virus, designed to selectively infect, replicate in, and destroy cancer cells. The key modifications in the vaccine including 1) ICP34.5 gene deletion, wich enhances tumor selectivity by restricting viral replication to tumor cells and prevents viral replication in healthy cells while allowing it in tumor cells. 2) ICP47 gene deletion, which enhances immune response by improving the presentation of tumor antigens to the immune system, facilitating immune recognition and attack on the cancer cells. 3) Insertion of immune regulatory element Granulocyte Macrophage Colony Stimulating Factor (GM-CSF), which promotes immune activation, encouraging the recruitment and activation of immune cells to target and destroy tumor cells.
Vaccinia virus can also be engineered as oncolytic virus by mutation of Thymidine Kinase (TK) and Vaccinia Growth Factor (VGF) to attenuate the pathogenicity and increase tumor-specific replication. An engineered vaccinia virus expressing GM-CSF and showed promising clinical efficacy in Phase I and Phase II trials.
Vesicular stomatitis virus is a negative single strand enveloped rhabdovirus. The enveloped glycoprotein mediates binding to tumor cells via cellular receptors, such as LDLR and LDL-like receptors.
Measles virus is a negative single strand RNA enveloped paramyxovirus. Live attenuated measles virus can be developed for oncolytic use. Measles virus hemagglutinin protein can bind to cellular receptors such as CD46, SLAM receptor and nectin-4 receptor.
|
|
|
| Measles viruses. (Source from Public Health Image Library (PHIL), distributed in Public Domain) | |
