A review published in The Lancet traces decades of experiments on these agents, capable of infecting and killing diseased cells, used to treat some neoplasms. Where are we at? And what makes this therapy so interesting?
We fear them considering them enemies to be defeated. But today oncologists are trying to add them to the arsenal of “therapeutic weapons” for treating cancer. Let’s talk about virus oncolitici: a review published, in September, in the 406 edition of The Lancet traces decades of studies on these agents, natural or engineeredcapable of selectively replicating in tumor cells and stimulating the immune system to recognize and destroy them.
What are oncolytic viruses
Table of Contents
“And virus oncolitico enters tumor cells through a specific key e activates cell death processes from the inside. In this way it releases fragments of the tumor which become “flags” recognizable by the immune system. This is how our organism learns to better identify and attack diseased cells” explains Mario Scartozziprofessor of Oncology at the University of Cagliari.
The idea started in the 1960s, when the Latvian immunologist Aina Muceniece observed that some echoviruses (positive single-stranded RNA enteroviruses) were capable of infecting and destroying melanoma cells, a neoplasm with a high infiltrative capacity. One of these viruses, ECHO-7, inoculated into a small group of patients with advanced stage cancer, proved capable of reducing the severity of the disease. The result was greeted with caution, but paved the way for subsequent studies on more representative samples of the population.
Ten years of progress
The authors of review they highlight the main historical stages that they see virus oncolitici used as drugs: since FDA approval in 2015 talimogene laherparepvec (derived from Herpes simplex type 1) for advanced melanoma, to that of teserpaturevalso a modified Herpes simplex type 1, in Japan in 2021 for highly malignant gliomasuntil nadofaragene firadenovecderived from a adenovirus, approved in the United States in 2022 for bladder cancer non-muscle invasive resistant to Bacillus Calmette-Guérin (the treatment of choice). «In addition to selectively targeting tumor cells, oncolytic rmake the microenvironment more visible to the immune system, amplifying the effect of current immunotherapy treatments. The combinations with already available immunotherapies show encouraging signs, especially in refractory patients, opening up scenarios that were unthinkable until recently”, he continues Scartozzi.
The security issue
While the evidence in the laboratory is exciting, viruses can mutate, as the experience with SARS-CoV-2 (a coronavirus) has shown. They return to oncolyticthe concomitant administration of drugs could enhance its spread, involving cells not yet affected by the neoplasm. Furthermore, paradoxically, the viral concentrations needed to lyse the tumor could be high enough to damage healthy cells.
The indissoluble link with traditional therapies
The interactions of virus oncoliticiSometimes they can be interesting. A key advantage comes from those with inhibitors of checkpointdrugs that counterattack the strategies adopted by cancer to proliferate. Under normal conditions, the immune system imposes brakes so that i T lymphocytes do not act in an irregular manner, with the risk of damaging healthy tissues. Over time, neoplastic cells have refined strategies to escape these controls. «When combined with the virus oncolitici, these drugs have shown that they can reactivate the immune system against the tumor”, he underlines Scartozzi. Radiotherapy and chemotherapy can also increase its effectiveness, stimulating the immune system and reducing the risk of resistance.
“This is still early and limited data, but it is worth investing in.” Future challenges are to develop more precise and heterogeneous studies of viral efficacy. Researchers consider it advisable the use of viruses in the initial stages of the disease (neoadjuvant and adjuvant therapy), in fragile patients or with multiple comorbidities, or in difficult-to-reach tumors, such as those that cross the blood-brain barrier. Finally, Artificial Intelligence has the potential to make tests more reliable, faster and faster. Curious how, in medicine, enemies can transform into allies.
