New research has shown that a oncolytic virusnamely that it fights cancer, in combination with immunotherapy, offers new hope for all those affected by resistant tumor forms.
The results of the study have been published in the scientific journal Cancer Cell.
Oncolytic virus in combination with immunotherapy: a new frontier in the fight against cancer
The human body’s immune system has evolved to safeguard the body from an extremely diverse number of potential threats. Among these have been found bacterial diseases, including plague, cholera, diphtheria, Lyme disease, and viral infections such as influenza, Ebola virus and SARS CoV-2.
Despite the impressive power of the immune system’s complex defense network, one type of threat is particularly difficult to combat. This occurs when the body’s native cells become rogue cells, leading to the development of cancer. Although the immune system often tries to rid the body of malignant cells, its efforts are often thwarted as the disease progresses uncontrollably.
The new treatment involving an oncolytic virus in combination with immunotherapy causes the cancer cell to be surrounded by immune T cells enhanced with an oncolytic virus. This combination of immunotherapy and virotherapy, using the myxoma virus, offers new and encouraging perspectives in resistant tumors. Research authors Grant McFadden, Masmudur Rahman, together with their team of collaborators, have proposed a new line of attack that has shown promising results.
Combining an oncolytic virus with immunotherapy involves the exploitation of two methods that have each shown remarkable success against certain types of cancer. The study showed how oncolytic virotherapy, a technique that uses cancer-fighting viruses, can work by enhancing already known immunotherapy techniques, increasing the immune capacity to effectively target and destroy cancer cells.
The oncolytic virus represents an exciting new avenue for cancer therapy. These viruses have the extraordinary ability to hunt and kill cancer cells leaving the sanr cells unharmed, as well as improving the immune system’s ability to recognize and break down cancer cells.
One such virus, known as myxoma, is the focus of current research and an area of expertise for the research team. The study shows that the use of T cells infected with the myxoma oncolytic virus can induce a form of cancer cell death not previously observed. Known as autosis, this form of cell destruction may be particularly useful against solid tumors that have been shown to be resistant to treatment with various forms of cancer therapy, including immunotherapy alone.
“This work affirms the enormous potential of combining virotherapy with cell therapy to treat currently intractable cancers,” he said. McFadden, who directs the Biodesign Center for Immunotherapy, Vaccines and Virotherapy at Arizona State University.
The immune system is made up of a series of specialized cells designed to patrol the body and respond to any attacks. The system is involved in a relentless arms race against pathogens, which evolve sophisticated techniques to try to outsmart the immune defenses, spread through the body to cause disease. Cancer presents a unique challenge to the immune system as cancer cells often lack the identifying cellular characteristics that allow the immune system to attack them and distinguish them from healthy ones.
Cancer cells can further short-circuit immune efforts to hunt and destroy them, through a series of evasive strategies. The researchers’ intent is to help the immune system overcome the infamous cancer disguise tactics by developing new experimental techniques, such as combination with an oncolytic virus, belonging to a category known as adoptive cell therapy or ACT.
These approaches often involve removing a collection of cancer-fighting white blood cells known as T cells, changing their search and destruction abilities, and re-injecting them into patients. Two forms of ACT immunotherapy are described in the new study: CAR T cell therapy (CART) and T cell receptor engineering (TCR). The basic idea in each case is the same: to treat cancer with activated T cells extracted from the patient.
The development of these therapies has been nothing short of revolutionary, and some cancer patients facing gloomy prospects have achieved remarkable healings after using immunotherapy. But techniques such as CART and TCR still have their limitations and are often ineffective against advanced solid tumors. In these cases, cancer cells often manage to evade destruction by T cells by downregulating or losing the surface antigens or MHC proteins that T cells use to identify them.
The new study highlights the ability of immunotherapy when coupled with an oncolytic virus capable of breaking through the wall of cancer resistance, in particular using T lymphocytes with myxoma. The oncolytic myxoma virus can directly affect and kill cancer cells but more usefully it can induce an unusual form of T-cell-directed cell death known as autosis. This form of cell death increases two other forms of programmed death of tumor cells induced by T lymphocytes, known as apoptosis and pyroptosis.
During myxoma-mediated autosis, cancer cells near those targeted by therapy are also destroyed in a process known as bystander killing. This effect can considerably increase the aggressive eradication of tumor cells by dual therapy with oncolytic virus even in solid tumors notoriously difficult to treat.
Combined oncolytic virus-immunotherapy therapy therefore has the potential to transform so-called “cold tumors”, which fly under the immune system’s radar, into “hot tumors” that immune cells can identify and destroy, allowing CAR T or TCR lymphocytes to enter the tumor environment, proliferate and activate.
“We are on the verge of discovering new aspects of the myxoma virus and oncolytic virotherapy,” explained Rahman. “Furthermore, these findings open the door for testing cancer-killing viruses with other cell-based anticancer immunotherapies that can be used in cancer patients.” The ability to radically redesign an oncolytic virus such as myxoma to target a range of resistant cancers provides a new frontier for the treatment of this devastating disease.
the Professor Fabrizio Pregliascovirologist of the University of Milan and medical director of the IRCCS Galeazzi Orthopedic Institute of Milan, regarding the use of an oncolytic virus to fight cancer, said: “”Viruses oncolytics they are genetically manipulated organisms to specifically attack cancer cells, which have the characteristic of replicating very quickly. In this way they they affect the tumor, sparing healthy cells and stimulating the immune system to produce a response against itself“.
Gabriella Campadelli-Fiume, Professor of Microbiology at the University of Bologna, who together with Pierluigi Lollini’s research group conducted the study on oncolytic viruses in mice, said: “Viruses are small specialized machines to kill the cell. The virus’ mission is to penetrate inside the cell and replicate itself: in doing this, the virus destroys the cell to propagate itself ”.
Regarding the approach with the oncolytic virus, Professor Campadelli-Fiume specified: “This approach does not want to weaken the virus, but simply make it specific to cancer cells”.
Scientists from the City of Hope Cancer Research and Treatment Center in Los Angeles and the Australian Biotechnology Society Imugene Limited are developing a good virus. It is a oncolytic virus, i.e. a virus that preferentially infects and kills cancer cells. Is called Vaxinia (CF33-hNIS) and, after obtaining positive pre-clinical results, the researchers announced that they had injected the drug into the first patient in the Phase 1 clinical trial.
Daneng Li, one of the researchers involved, said: “Our previous research has shown that oncolytic viruses can stimulate the immune system to respond and kill cancer, as well as make it more responsive to other immunotherapies. Now is the time to further enhance immunotherapy, and we believe CF33-hNIS has the potential to improve outcomes for our patients in their battle with cancer. “
work of Evelyne Tassonebiologist and researcher at the Pasteur Italia Institute, Cenci Bolognetti Foundation (Rome), thanks to the support of a research grant from the Umberto Veronesi Foundation,said her about the use of the oncolytic virus: “Unlike common viruses, oncolytic viruses infect and kill cancer cells specifically, leave healthy cells intact and are able to induce an immune response against tumors by contributing to their eradication “.
It is therefore a selective weapon against cancer: “However, cancer cells can develop resistance to viruses and not respond to treatment. The project plans to identify which are the genes involved in resistence of pancreatic cancer cells to oncolytic viruses, using a combined approach of cell biology, molecular and bioinformatics ”.
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