Nav: Home

Researchers create viruses to selectively attack tumor cells

March 16, 2017

Scientists at the IDIBAPS Biomedical Research Institute and at the Institute for Research in Biomedicine (IRB Barcelona) lead a study in which they have designed a new strategy to get genetically modified viruses to selectively attack tumor cells without affecting healthy tissues. The study, published today by the journal Nature Communications, is part of Eneko Villanueva's work for his PhD and it is co-lead by Cristina Fillat, head of the Gene Therapy and Cancer Group at IDIBAPS, and Raúl Méndez, ICREA researcher at IRB Barcelona.

Conventional cancer treatment may cause undesirable side effects as a result of poor selectivity. To avoid them it is important that new therapies can efficiently remove cancer cells and preserve the healthy ones. One of the new approaches in cancer therapy is based on the development of oncolytic viruses, ie, viruses modified to only infect tumor cells. In recent years several studies have been focused on the development of viruses created by genetic engineering to maximize their anticancer effect but, as their potency increases, so does the associated toxicity. Limiting this effect on healthy cells is now the key for the application of this promising therapy.

An innovative and specific approach

In the study published in the journal Nature Communications, researchers from IDIBAPS and IRB Barcelona have developed an innovative approach to provide adenovirus with high specificity against tumor cells. "We have taken advantage of the different expression of a type of protein, CPEBs, in normal and tumor tissues", explains Raúl Méndez from IRB Barcelona.

CPEB is a family of four RNA binding proteins (the molecules that carry information from genes to synthesize proteins) that control the expression of hundreds of genes and maintain the functionality and the ability to repair tissues under normal conditions. When CPEBs become imbalanced, they change the expression of these genes in cells and contribute to the development of pathological processes such as cancer. "We have focused on the double imbalance of two of these proteins in healthy tissues and tumors: on the one hand we have CPEB4, which in previous studies we have shown that it is highly expressed in cancer cells and necessary for tumor growth; and, on the other hand, CPEB1, expressed in normal tissue and lost in cancer cells. We have taken advantage of this imbalance to make a virus that only attacks cells with high levels of CPEB4 and low CPEB1, that means that it only affects tumor cells, ignoring the healthy tissues," says Méndez.

"In this study we have worked with adenoviruses, a family of viruses that can cause infections of the respiratory tract, the urinary tract, conjunctivitis or gastroenteritis but which have features that make them very attractive to be used in the therapy against tumors," explains Cristina Fillat. To do this, it is necessary to modify the genome of these viruses. In the study researchers have inserted sequences that recognize CPEB proteins in key regions for the control of viral proteins. Their activity was checked in in vitro models of pancreatic cancer and control of tumor growth was observed in mouse models.

The oncoselective viruses created in this study were very sophisticated, being activated by CPEB4 but repressed by CPEB1. Thus, researchers achieved attenuated viral activity in normal cells, while in tumor cells the virus potency was maintained or even increased. "When the modified viruses entered into tumor cells they replicated their genome and, when going out, they destroyed the cell and released more particles of the virus with the potential to infect more cancer cells," says Fillat. She adds that, "this new approach is very interesting since it is a therapy selectively amplified in the tumor".

Since CPEB4 is overexpressed in several tumors, this oncoselective strategy may be valid for other solid tumors. Researchers are now trying to combine this treatment with therapies that are already being used in clinical practice, or that are in a very advanced stage of development, to find synergies that make them more effective.
-end-
Reference article:

Eneko Villanueva, Pilar Navarro, María Rovira-Rigau, Annarita Sibilio, Raúl Méndez, Cristina Fillat

Translational reprogramming in tumor cells can generate oncoselectivity in viral therapies

Nature Communications. DOI: 10.1038/NCOMMS14833

Institute for Research in Biomedicine (IRB Barcelona)

Related Cancer Articles:

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.
Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.
Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.
More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.
New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.
More Cancer News and Cancer Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Erasing The Stigma
Many of us either cope with mental illness or know someone who does. But we still have a hard time talking about it. This hour, TED speakers explore ways to push past — and even erase — the stigma. Guests include musician and comedian Jordan Raskopoulos, neuroscientist and psychiatrist Thomas Insel, psychiatrist Dixon Chibanda, anxiety and depression researcher Olivia Remes, and entrepreneur Sangu Delle.
Now Playing: Science for the People

#537 Science Journalism, Hold the Hype
Everyone's seen a piece of science getting over-exaggerated in the media. Most people would be quick to blame journalists and big media for getting in wrong. In many cases, you'd be right. But there's other sources of hype in science journalism. and one of them can be found in the humble, and little-known press release. We're talking with Chris Chambers about doing science about science journalism, and where the hype creeps in. Related links: The association between exaggeration in health related science news and academic press releases: retrospective observational study Claims of causality in health news: a randomised trial This...