Polish scientists have discovered a new mechanism that cancer cells use to trick the immune system. Cancer cells can send “malware” to the lymph nodes that block the action of the lymphocytes. Work is already underway on a therapy that uses this knowledge.
From the research of the team of prof. Jakub Gołąb from the Medical University of Warsaw, cancer cells can send tiny bubbles to the lymph nodes with a substance that suppresses the immune system’s response. Due to such a diversion – carried out not at the tumor site, but where the immune system responds – the body is less able to fight the rogue cells.
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This mechanism of tumor escape from immune surveillance was not known before. The results of the study – so far they concern ovarian cancer – appeared in the prestigious Nature Communications.
In cooperation with the Polish company OncoArendi Therapeutics, a compound has already been developed that is a candidate for an anti-cancer drug that will block these compounds that confuse the immune system. Thanks to this – as scientists count – the body will be able to stop the growth of the tumor. The compound is now in the preclinical research phase, but the first patients will receive it next year. It is hoped that this new approach to cancer therapy will help with various types of cancer – not just ovarian cancer.
T lymphocytes – our internal army that defends the body against pathogens and rogue cells – are activated in the lymph nodes. And this is where cancer cells – such as the ovary – try to reach with their actions. – We have shown that the tumor sends something like an e-mail 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 microbubbles (so-called exosomes) and let them into the lymphatic vessels. In the lymph nodes, these packages are unpacked and arginase is released. Meanwhile, this enzyme breaks down arginine – a substance necessary to activate T lymphocytes to fight. Due to the tumor, the lymphatic activity of the army is impaired in the barracks themselves – soldiers are not given a signal to attack.
Researchers know how to prevent cancer cells from manipulating the immune system. They have developed a compound that blocks the action of “malware”. Scientists 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 to restore normal T-cell function and inhibit tumor progression in a mouse model of ovarian cancer. This compound (as OATD-02) is in the phase of preclinical research, told PAP Dr. Roman Błaszczyk from OncoArendi Therapeutics. Prof. Gołąb adds that the Polish company will be the second company in the world next year to start clinical trials of arginase inhibitors. – This Polish compound is much more active than the one that was developed earlier in the USA – says prof. Pigeon.
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The researcher from the Medical University of Warsaw explains that the compound developed in the Polish company raises hopes for new therapies because arginase – “malware” – is produced by many types of cancer, not just ovarian cancer. It was previously known that this compound is produced by certain tumors of the central nervous system (neuroblastoma) and acute myeloid leukemia cells. – We were the first to describe the presence of arginase in microbubbles released into the body by ovarian cancer cells – adds prof. Pigeon. He explains that this was studied in ovarian cancer, but it is possible that similar mechanisms of hiding from the immune system exist in other types of cancer.
Prof. However, Gołąb emphasizes that the arginase inhibitor that Poles are working on does not cure mice from cancer. – He’s blocking tumor progression. This therapy is not enough to eliminate the tumor. We suppose that there is still something missing to stimulate this response. We already have a clue as to what the missing element may be – he says. However, he supposes that the work on this missing element will probably take several years.
– We could act several times faster if it were not for the public procurement law, which is so organized that it significantly extends the waiting time for the reagents we order – concludes Prof. Pigeon.