Oncolytic Virus Vaccines
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Weizmann 14, Tel Aviv, Israel
The term “oncolytic virus” refers to any virus that prefers to infect and/or kill cancer cells, while sparing normal cells. Oncolytic viruses can occur naturally or be genetically-modified from a human or non-human source. As research into alternative forms of cancer treatment continues, oncolytic viruses offer a most promising alternative modality for the successful treatment of cancer in case of failure of conventional anticancer medications.
Anti-cancer virotherapy was first conceptualized in 1960, after researchers noticed that some viruses (including polioviruses, adenoviruses, and herpes viruses) seemed to attack cancerous or mutated cells first.
Unfortunately, some of these viruses could be harmful and responsible for serious complications. As a result, research on virotherapy was shelved for several decades.
One of the first pioneers that introduced Newcastle disease virus (NDV), a safe poultry virus, for the treatment of cancer, was a Hungarian virologist named Laslo K. Csatary. During the first few years of the 21st century, advances in DNA and RNA mapping brought about new ways to accurately modify viral strains.
Hand-in-hand with new technologies for selective targeting of cancer cells and the ability to choose safer viruses, the use of oncolytic viruses is becoming an attractive and most promising new modality for cancer treatment.
Oncolytic viruses have special receptors that can attach themselves to the surface antigens that cover cancer cells. Through them, they can attach or enter these cells and infect them while leaving the surrounding healthy cells largely untouched.
The anti-cancer effects of oncolytic viruses are mediated by two independent mechanisms. First, after infecting the cell, the virus will hijack its reproduction capabilities to create new copies of itself. Eventually, it will kill the host cell through “apoptosis”. This will cause the cell to disintegrate, releasing thousands of virions (viral particles) into surrounding cancer cells and supporting blood vessels. After reaching the bloodstream, the virions can travel around the body and potentially infect other cancerous cells in distant organs. As such, oncolytic viruses can cause direct anti-cancer cytotoxicity.
Next, cancer cells or any of their secretory components “decorated” with viral antigens by oncolytic viruses can activate the immune system to react against other cancer cells, which are now expressing stimulatory new antigens. In other words, oncolytic viruses can turn non-immunogenic (“cold”) tumor cells into immunogenic (“hot”) tumor targets. Such a reaction can break the unresponsiveness of a patient’s immune system against cancer; ignoring cancer cells allows ongoing uncontrolled cancer cells proliferation and propagation.
Taken together, the use of oncolytic viruses can have a dual anti-cancer mechanism. The first one is direct virus-induced cytotoxicity; the second one is virus-induced anti-cancer immunotherapy against modified cancer cells.
Oncolytic viruses can also modify cryopreserved cancer cells or lysates of cancer tissue that can be used for the preparation of anti-cancer vaccines.
Yet, each one works in a slightly different way. Anti-cancer vaccines train the immune system to recognize and attack cancer cells now appearing as foreign or “non-self”. Because of this, once the immune system is activated against cancer, the therapeutic effect tends to last longer. Obviously, the availability of anti-cancer vaccines depends on the availability of fresh or cryopreserved tumor tissue or tumor-derived components.
To prolong or strengthen the potential therapeutic effects of oncolytic viruses, it is possible to combine oncolytic virus therapy with other forms of immunotherapy. Furthermore, the anti-cancer effects induced by oncolytic viruses can be amplified through the administration of several medications available at Biotherapy International. These can act in synergy with oncolytic viruses to increase the direct cytotoxicity induced by the viruses.
For example, to further amplify the anti-cancer effects induced by oncolytic viruses, any of the immunotherapy protocols available at Biotherapy International can be used, including checkpoint inhibitors, down regulation of regulatory T cells, myeloid-derived suppressor cells and tumor associated macrophages. Immunotherapy can also be amplified by the use of cytokine-mediated immunotherapy (CMI), which consists of outpatient administration of interleukin 2 and alpha interferon to activate a patient’s T cells and natural killer (NK) cells. Interferons can also increase cancer cells’ expression of potentially immunogenic cell surface antigens.
Oncolytic viruses can be used in two different ways:
The first method depends on the availability of cancer tissue or other tumor-derived components. This is why the use of lysates from cryopreserved tumor tissue remains the preferred method. However, this requires the patient to proactively preserve tumor samples during the initial diagnosis and store them at a tumor bank.
Cryopreserving a tumor sample at ultra-cold temperature ensures it stays as close as “fresh” as possible. This keeps all the information stored in the tumor’s DNA intact.
If standard anti-cancer treatments (such as chemotherapy or radiotherapy) fail, the cryopreserved tumor sample can help us prepare a customized anti-cancer vaccine. This will teach your immune system to recognize the DNA in your tumor as “non-self” and aggressively fight it as it would fight an infection.
If the tumour is not in an easily accessible location, or if it was already removed, it is also possible to use blood-derived cancer components. Blood samples often contain circulating tumour cells, excretory extracellular vesicles or exosomes. These can all be used as a source of cancer antigens, and then be used to manufacture an anti-cancer vaccine.
Ideally, blood samples will need to be harvested and cryopreserved before initiating any conventional oncological treatment (like chemotherapy). This will increase the chances of finding cancer antigens amidst the blood tissue.
It is impossible to know from the start whether cancer will become recurrent or if it will metastasize. Most cancers respond well to conventional treatments. When they don’t, additional rounds of chemotherapy or radiotherapy are mainly ineffective in eliminating cancer to the last cell.
When a patient is first diagnosed with cancer, we all expect advanced treatments like immunotherapy won’t be necessary. If they do, having a tumor sample stored in a tumor bank can make a massive difference in the range of treatments available.
Contact us using the form below. One of our team members will contact you and schedule a video call with you and your attending physician.
During this call, we will explain the necessary procedure to reserve a tumor sample during a biopsy, store it, and send it to our tumor bank.
It is important to begin the process before the initial biopsy or cancer-removal surgery. The surgeon needs to be notified ahead of time in order to preserve as much of the original tumor tissue as he can.
The tumor sample can be stored in 2-ml or 5-ml sterile tubes, made from a material that can withstand cryopreservation. If this is not available, the surgeon can also use a 50-ml tube with a small amount of saline solution.
Then, the tumor needs to be transported to Tel Aviv via our courier. During the journey, it should be kept on cold ice at ultra cold temperatures (either a deep-freeze refrigerator at -80°C, or a liquid nitrogen refrigerator at -196°C).
