Polish discovery: Cancer sends "malware" to lymph nodes
Polish scientists have discovered a new mechanism that cancer cells use to deceive the immune system. Cancer cells can send "malware" to the lymph nodes in order to block lymphocytes. Work on therapies using this knowledge is already in progress.
According to the research of Prof. Jakub Gołąb`s team of from the Medical University of Warsaw, cancer cells can send small vesicles to the lymph nodes. These vesicles contain a substance that blocks the immune system`s response. As a result of this diversion, carried out not in the place of the tumour, but where the immune response begins, the body is less capable of fighting the rebellious cells.
This mechanism of tumour escaping the surveillance of the immune system has not been known before. The results of the study (concerning ovarian cancer for now) appeared in the prestigious journal https://www.nature.com/articles/s41467-019-10979-3https://www.nature.com/articles/s41467-019-10979-3.
A compound that is a candidate for an anticancer drug that blocks these compounds confusing immune systems has already been developed in cooperation with the Polish company OncoArendi Therapeutics. Scientists hope that as a result, the body will be able to stop the development of cancer. The compound is now in the preclinical trial stage, the first patients will receive it next year. There is hope that this new approach to cancer therapy will help in various types of cancer, not only in ovarian cancer.
T cells - our internal army that defends the body against pathogens and rebellious cells - are activated in the lymph nodes. And that is the place that cancer cells - for example ovarian cancer - try to reach with their activities. "We showed that the tumour sends something like an email with malware to the immune system" - compares Prof. Jakub Gołąb. He says that cancer cells produce a certain enzyme - arginase. They pack this substance into special vesicles (called exosomes) and let them into the lymphatic vessels. These packages are unpacked in lymph nodes and arginase is released. This enzyme breaks down arginine - a substance necessary to launch T cells. Due to the cancer`s diversion, the lymphatic army is stuck in the barracks - soldiers do not receive a signal to attack.
Researchers know how to prevent cancer cells from manipulating the immune system. They have developed a compound that blocks the operation of "malicious software". Researchers from the Polish company OncoArendi, in cooperation with the team from the Medical University of Warsaw, invented a new, very active arginase inhibitor - OAT-1746. "It has been shown that it restores normal T cell function and inhibits tumour progression in a mouse model of ovarian cancer. This compound (as OATD-02) is in the phase of preclinical studies" - says Dr. Roman Błaszczyk from OncoArendi Therapeutics.
Prof. Gołąb adds that next year, the Polish company will be the second in the world to start clinical trials of arginase inhibitors. "This Polish compound is much more active than the one previously developed in the US" - says Prof. Gołąb.
The researcher from the Medical University of Warsaw explains that the compound developed in the Polish company gives hope for new therapies because arginase - the "malicious software" - is produced by many types of cancer, not just ovarian cancer. This compound is produced by some central nervous system cancers (neuroblastoma) and acute myeloid leukemia. "We were the first to describe the presence of arginase in vesicles released into the body by ovarian cancer cells" - adds Prof. Gołąb. He explains that this mechanism was studied on the example of ovarian cancer, but it is possible that other types of cancer have similar mechanisms of hiding from the immune system.
Prof. Gołąb emphasizes that the arginase inhibitor, on which Polish researchers are working, does not allow to cure cancer in mice. "It blocks the progression of the tumour. This therapy is not enough to eliminate the cancer, we suppose that there is something missing that would stimulate the response. We have our suspicions as to what this missing piece could be" - he says. He suspects that work on this missing element will probably take several years.
"We could work several times faster, if it were not for the public procurement law. The way it is organized, it significantly extends the waiting time for the reagents that we order" - concludes Prof. Gołąb.
PAP - Science in Poland, Ludwika Tomala
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