29 April 2022

Mechanism of oncolysis

Scientists have figured out how a plant virus effectively fights cancer

Svetlana Maslova, Hi-tech+

In many studies, the cowpea mosaic virus has shown promising results in the treatment of various types of tumors and metastases, but until now scientists had only a general idea of the mechanism of the virus attack on cancer cells. A comparative experiment allowed us to determine the processes inside the body that explain its phenomenal properties.

Over the past few years, scientists from the University of California, San Diego have been studying cowpea mosaic virus (CPMV) as a means for cancer immunotherapy. For example, preclinical experiments have already shown that nanoparticles created from the cowpea mosaic virus prevent the development of metastases in tumors of the mammary glands, lungs, melanoma, colon cancer and a number of others. Meanwhile, the exact reasons for this success remained a mystery.

Scientists knew the main thing: CPMV is not dangerous for mammals and, when injected directly into the tumor, serves as a bait for immune cells that perceive the virus as a foreign agent and attack it. As a result, this leads to the rapid suppression of cancer and its metastases in the body, and also forms immune memory to prevent relapse.  Now they decided to analyze the effects of CPMV with two other plant viruses of the same family, identical in shape and size. One had a similar RNA sequence and protein composition, and the other was similar only in structure. The findings of the experiment are reported by the press release of Researchers Shed Light on Why a Certain Plant Virus Is So Powerful at Fighting Cancer,

article by Beiss et al. Cowpea Mosaic Virus Outperforms Other Members of the Secoviridae as In Situ Vaccine for Cancer Immunotherapy published in the journal Molecular Pharmaceuticals – VM.

Three groups of mice with melanoma were injected with viruses in three doses with an interval of seven days.

After CPMV treatment, the mice had the highest survival rate and the smallest tumors. Their growth stopped about four days after the second dose.

CPMV.jpg

Then the scientists extracted immune cells from the spleen and lymph nodes of the animals and began to look for differences. At first it became clear that all three plant viruses activated toll-like receptors on the surface of immune cells. However, upon further observation, only CPMV activated an additional receptor that produced cytokines — pro-inflammatory proteins that enhance the anti-cancer response of the immune system.

The level of cytokines remained high for a long period, the authors said, while when treated with other viruses, it quickly peaked and began to fall. That is, a long-term immune response is also an important difference and advantage of CPMV.

Scientists recognize that the results obtained are extremely important for improving cancer immunotherapy, but have raised even more questions. Further studies will have to find out what happens to the viral CPMV nanoparticle inside cells and why, unlike other viruses, its RNA is well recognized.

Another cancer treatment strategy uses bacteria. However, in this case, scientists, on the contrary, hide them from the immune system so that they safely reach the tumor and deliver the medicine to it.

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