Therapeutic Retroviruses to the Rescue? Using Viruses Engineered to Fight Cancer
When many hear the word “virus,” they don’t immediately think “anticancer therapy;” however, researchers in the field are trying to change this thought process. In October 2015, the FDA approved the injectable formulation, Imlygic, a virus-based therapy for the treatment of melanoma lesions in the skin.1 The therapy was engineered from the herpes simplex virus 1 and modified to prevent the attenuation of the virus by selectively binding to and destroying cancer cells. Additionally, the binding of the virus-based drug induced the secretion of cytokine GM-CSF, a protein that initiates an immune response to support the destruction of cancer cells. Doctors administer the therapy by directly injecting the virus into melanoma lesions, where it replicates inside of cancer cells and eventually leads to cancer cell death and cell rupture.2
Expanding Viral Treatment to Diseases Beyond Melanoma
Currently, Imlygic has been approved for the treatment of melanoma alone. However, its use could be expanded in the treatment of a variety of other diseases if there was a way to directly inject it into tumors or prevent the immune system from attacking the engineered viruses as they travel to a tumor site in the body. In cases where a tumor cell is not visible and cannot be easily injected, one option is for the therapeutic retroviruses to “hitch” rides on red blood cells (RBCs). To do so, they must be attracted to and bind selectively to RBCs. In the presence of the tumor cell, though, the greater affinity of the viral ligand for the cancer cells should induce it to transfer from the RBC to the tumor and thus exert its anticancer effects there. Given that the cell death-inducing activities of Imlygic is specific to cancer cells, the use of therapeutic retroviruses like these should not compromise the function of RBCs.
One particularly exciting area for treatment is glioblastoma tumors, which arise from astrocytes in the brain. These tumors are often highly malignant and can be especially aggressive.3 Furthermore, there are no curative treatments in part due to the difficulty of reaching these tumors often lodged deep in the brain.4 If there were a way to selectively target the cancerous glioblastoma cell with viral therapies, such technology could revolutionize the treatment of this very difficult cancer and open the door to the treatment of other difficult to reach cancer cells such as colon and rectal cancers and ovarian cancers.5
In considering how to create therapeutic retroviruses capable of jumping from one cell to a cancerous one, research scientists must invest a significant amount of time and effort into generating large antibody libraries capable of elucidating the shape and structure of proteins that can bind most specifically and tightly to cancer cells to induce the virus to fall off RBCs. Additionally, antibodies that are capable of binding the therapeutic retroviruses to RBCs to begin with should be tight, but not tighter than the interactions that occur between the therapeutic retroviruses and the cancer cell.
Other considerations include determining how to ensure that the virus does not induce immunogenicity as it travels on RBCs. Viruses and microorganisms are targeted for destruction by leukocytes and each person who uses therapeutic retroviruses as forms of treatment is susceptible to having his or her form of treatment attacked by his or her own cells. Thus, determining the T-cell receptor profile for different individuals and modifying the viral coat of the virus, could decrease or eliminate the chances that the therapeutic retroviruses are attacked by immune system cells, thus decreasing the potency of anticancer therapies.
Tools of the Trade to Advance Cancer Treatments
To develop new therapeutic retroviruses, analytic software is the way forward. Using digital offerings such as BIOVIA Biologics Solution, researchers can make use of predictive analysis to identify how proteins fold in the presence of various cell surface markers, for example, that might make the therapeutic retroviruses more or less sensitive to cancer cells or carrier proteins, respectively. Additionally, software can assist in assay development and activity analysis, information that is essential to test whether or not altered retroviruses are working and effective.
Currently, neurological cancers remain among the most untreatable forms of the disease so using predictive analytics to change the size of therapeutic retroviruses, might then enable them to cross the blood brain barrier in order to attack cancer cells. Either way therapeutic retroviruses could prove an essential component of tomorrow’s anticancer treatments. Contact us today to learn more about how our offerings can support these efforts.
- “FDA approves first-of-its-kind product for the treatment of melanoma,” October 27, 2015, http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm469571.htm ↩
- “Hitchhiking Virus Escapes Immune System to Fight Cancer,” June 19, 2012, http://www.healthmap.org/site/diseasedaily/article/hitchhiking-virus-escapes-immune-system-fight-cancer-61912 ↩
- “Glioblastoma,” 2014, http://www.abta.org/brain-tumor-information/types-of-tumors/glioblastoma.html?referrer=https://www.google.com/ ↩
- “Glioblastoma Multiforme Treatment and Management,” December 11, 2015, http://emedicine.medscape.com/article/283252-treatment ↩
- “The 10 Deadliest Cancers and Why There’s No Cure,” September 10, 2010, http://www.livescience.com/11041-10-deadliest-cancers-cure.html ↩