Attacking gynecological cancers with a biopharmaceutical based on a genetically modified virus

A biopharmaceutical based on a genetically modified virus has shown strong antitumor activity against various gynecological cancers in laboratory tests.

On the way to obtaining a treatment that improves the life expectancy of women with different forms of gynecological cancer, especially ovarian cancer, which is one of the most lethal, some scientists from the Leloir Institute Foundation (FIL) have shown, on tumor samples and malignant cells obtained from patients with advanced ovarian, uterine, and cervical cancer, the therapeutic efficacy of a special type of genetically modified virus to kill tumor cells.

The achievement is the work of a team that includes Ana Alfano and María Verónica López, from the Laboratory of Molecular and Cellular Therapy (LTMC) directed by Osvaldo Podhajcer and which depends on the Fundación Instituto Leloir (FIL) in Argentina.

The use of the genetically modified virus also showed an immune-mediated antitumor effect in mice that slowed the progression of untreated tumors.

“AR2011 is a unique oncolytic adenovirus in its class because it is capable of detecting the tumor microenvironment and activating its attack mechanism only in that environment, which ensures that it generates fewer adverse effects than conventional treatments,” Podhajcer told CyTA Agency. -Leloir. The researcher, from the National Council for Scientific and Technical Research (CONICET), explained that his group developed AR2011 in 2017 and then CONICET and FIL licensed the patent to an American start-up called Unleash Immuno Oncolytics, which will try to bring improved versions of AR2011 to a clinical trial. In the meantime, the group is conducting additional studies like the ones just published.

“These new results show that, indeed, AR2011 would be a good candidate to advance with studies in humans, even combinable with the chemotherapy currently used in the treatment, and especially useful in advanced stages of the disease,” said López. .

CONICET researchers María Verónica López and Osvaldo Podhajcer, from the Laboratory of Molecular and Cellular Therapy of the Leloir Institute Foundation, co-authors of the study. (Photo: Leloir Institute Foundation / CONICET)

beyond the laboratory

Every year, more than a million women in the world are diagnosed with some type of gynecological cancer; among them, one of the most common and dangerous is ovarian. Due to the late appearance of symptoms and the absence of early detection methods, this type of cancer is often diagnosed in advanced stages. Although patients initially respond to chemotherapy, most quickly become resistant to treatment and the disease recurs. Thus, at present the rates of survival or 5-year survival are less than 50%.

In this scenario, the search for innovative approaches to treat this disease, which in Argentina is diagnosed annually in 2,200 women, becomes urgent and one of the strategies being evaluated is the use of genetically modified oncolytic viruses to exclusively attack and eliminate tumor cells, decreasing the adverse effects on normal tissues.

That is the case of AR2011, where an adenovirus (one of the viruses that causes the cold or common cold) was used, which was genetically modified in the LTMC so that it attacks cancer cells, but not healthy ones.

The LTMC directed by Podhajcer at FIL has been working for 25 years in different aspects related to the fight against cancer. On the one hand, the group seeks to design and carry out tests on preclinical models of biopharmaceuticals generated in the LTMC itself, with potential application in advanced disease. On the other, it carries out studies to identify genomic markers in patient samples that make it possible to predict their evolution and response to treatment.

The project began several years before the pandemic but had to be interrupted when the LTMC team decided to dedicate their energies to collaborating with the health emergency. 99% of the experiments were finished by 2020, but for more than two years these scientists were working on generating a vaccine against COVID-19. A few months ago they resumed the study, thoroughly analyzed the data and completed the work.

The study is titled “In Vitro and In Vivo Efficacy of a Stroma-Targeted, Tumor Microenvironment Responsive Oncolytic Adenovirus in Different Preclinical Models of Cancer”. And it has been published in the academic journal International Journal of Molecular Sciences. (Source: CyTA-Leloir Agency)