How Viruses Can Be Powerful Weapons for Curing Cancer

Viruses have always been seen as major health villains – a notion that is even stronger during a pandemic like the one we are experiencing, in which the cause of Covid has been associated with 20 million deaths so far.

But within oncology, a specialty of medicine that deals with cancer, some of these infectious agents are increasingly seen as allies: viruses can become a valuable tool to treat a range of tumors, experts point out.

Currently, several research groups are evaluating the possibility of using so-called oncolytic viruses as a way to directly attack cancer cells or to encourage a more robust immune system response against these diseased units.

The most recent example of this scientific endeavor is CF33-hNIS Vaxinia, a virustherapy developed by City of Hope, a hospital located in the United States, and Australian pharmaceutical company Imugene.

The product brings infectious agents from the same family as smallpox that have been modified in the laboratory to specifically attack tumor cells.

In pre-clinical tests, carried out with samples of cells and guinea pigs, this strategy was able to reduce several types of tumors, such as those that appear in the large intestine, lungs, breasts, ovaries and pancreas.

It remains to be seen whether this same effect occurs in humans. In late May, scientists began clinical trials, which involve volunteers.

In the first phase of the studies, which will involve 100 patients, the goal is to check whether the product, injected directly into the tumor or applied through infusions into a vein, is really safe and does not cause side effects.

The results of the experiment should come out within 24 months.

“We hope to harness the promise of virology and immunotherapy to treat a wide variety of cancers that are deadly,” predicts cancer surgeon Yuman Fong, one of the creators of virustherapy at City of Hope, in a press release.

double action

To understand how virustherapy works in practice, we first need to know how viruses work in nature.

Viruses are extremely simple pathogens whose only function is to invade the cells of a living being and “hijack” that biological machinery to create new copies of itself.

These new copies, in turn, will repeat the process for the duration of the infection. In this rite of invasion, kidnapping and replication, the cells affected by the virus do not resist and die.

From the observation of this viral mechanism, some scientists began to speculate: is it not possible to use the same principle to attack only the cells that form the tumor?

This is the basic premise of virustherapy: finding in nature, or developing in the laboratory, pathogens that specifically target cancer cells. And, by investing in this type of treatment, it is possible to obtain two different positive effects.

“The first one is to make the virus invade the sick cell and kill it”, explains immunologist Martin Bonamino, a researcher at Inca (National Cancer Institute).

“The second is that some of these modified viruses carry specific genes that generate antibodies and stimulate the patient’s own immune system to recognize the tumor and start attacking it”, adds the specialist, who also works at FioCruz (Fundação Oswaldo Cruz).

This dual action can be further potentiated with the use of other remedies together. One possibility is to combine oncolytic viruses with immunotherapy, a type of treatment that encourages the immune system to identify and fight cancer.

But how is it possible to guarantee that these therapeutic viruses will only infect tumor cells and spare the healthy units of the organism? This is where biotechnology and genetic engineering come into play.

“The idea is to find pathogens that have an affinity with cancer cells and act specifically on them”, contextualizes clinical oncologist Vladmir Cordeiro de Lima, from AC Camargo Cancer Center, in São Paulo.

decades of work

The first successful cancer virus therapy proposal was T-VEC, a drug approved by the US regulatory agency in 2015 (it is not available in Brazil at the moment).

It is a therapeutic resource indicated for cases of melanoma, a type of skin cancer that is usually aggressive. Since then, several other studies in this area have been initiated. Some of them are even underway in Brazil.

Two different research groups, one at USP (University of São Paulo) and another at Unicamp (State University of Campinas), for example, are studying whether the Zika virus can be used as a treatment for some types of cancer that affect the nervous system. central.

The idea came from the observation that this pathogen, behind a serious public health problem in the country since 2015, has a “preference” for attacking the cells that make up the brain and nerves – this, by the way, explains the fact of him being behind microcephaly in babies during pregnancy.

The first results, obtained in 2018 from experiments with guinea pigs, were encouraging: Zika actually reduced the size of tumors in the nervous system in a significant portion of the animals.

Sought by BBC News Brazil, geneticist Mayana Zatz, who leads research on Zika at USP, says that investigations into the potential oncolytic virus are ongoing.

“We are working on several fronts. We are looking, for example, for different strategies to obtain a modified Zika in the laboratory”, he explains.

The idea is that these genetic alterations made to the “original” virus allow for an intensified response to treatment, to obtain even superior results.

“We are also injecting the unmodified virus into dogs diagnosed with brain tumors and monitoring the clinical and neurological evolution of the cases”, adds the researcher, who coordinates the Center for Studies in Human Genome and Stem Cells at USP.

While knowledge in the area gradually advances, Bonamino emphasizes the importance of basic scientific research so that innovations such as oncolytic viruses can become a reality.

“These treatments are the result of many years of study, which made it possible to unravel the basic mechanisms of the viruses and create genetic engineering techniques”, he points out.

Cordeiro de Lima, in turn, understands that virustherapy may become, in the future, an auxiliary tool in the treatment of many tumors.

“There is great potential for it to be combined and integrated with other strategies, as a way to increase the spectrum of patients who benefit from cancer treatments”, concludes the doctor.