Development of a promising therapeutic strategy for pancreatic cancer

PARIS, Mar. 25. (Benin News) –

A new strategy developed by scientists at Albert Einstein College of Medicine at Yeshiva University in the United States has made pancreatic tumors visible to the mouse immune system and vulnerable to immune attack, reducing thus 87% cancerous metastases. That’s what they report online in the journal “Science Translational Medicine.”

“Current checkpoint inhibitor drugs work well against some types of cancer, but they rarely help people with pancreatic cancer,” says Claudia Gravekamp, ​​PhD, author of the paper, associate professor of microbiology and d Immunology to Einstein and member of the Albert Einstein Cancer Center designated by the National Cancer Institute.

The problem is that pancreatic tumors are not ‘foreign’ enough to attract the attention of the immune system and can usually suppress any immune response that occurs,” she explains. Essentially, our new therapy makes immunologically “cold” tumors hot enough for the immune system to attack and destroy.

Dr. Gravekamp’s therapeutic strategy takes advantage of the fact that virtually everyone is vaccinated in childhood against tetanus, a serious disease caused by a toxic protein secreted by the bacterium “Clostridium”.

Thanks to their tetanus-specific memory T cells, which circulate in the blood throughout life, vaccinated people will have a strong immune response if they are subsequently exposed to the very rare tetanus toxin. The researchers actually triggered a potent and specific immune response against pancreatic cancer cells by infecting them with bacteria that release tetanus toxin into the cells.

Using the same tetanus vaccine given to humans, the researchers vaccinated mouse models of pancreatic cancer (that is, mice with human pancreatic tumors). They then fused the gene coding for tetanus toxin with the non-pathogenic bacterium “Listeria monocytogenes”, which is very good at infecting cells and spreading in tissues. Finally, to infect and “tetanise” the tumours, they injected the bacteria with their tetanic genetic loads into previously vaccinated tumor-bearing mice.

“Listeria bacteria are quite weak and are easily eliminated by the immune system of humans and animals, except in tumor sites,” says Gravekamp. Our treatment strategy takes advantage of the fact that pancreatic tumors are so good at suppressing the immune system in order to protect themselves. This means that only Listeria bacteria present in the tumor region survive long enough to infect tumor cells in the pancreas and healthy cells are not infected.

Once the Listeria bacterium infected the tumor cells, its tetanus toxin genes expressed the tetanus toxin protein inside the tumor cells, triggering a strong immune response. Tetanus toxin activated preexisting tetanus-specific memory T cells, causing CD4 T cells to attack and kill infected tumor cells.

T cell responses were enhanced by the addition of low doses of gemcitabine (a chemotherapy drug that reduces immune suppression). The treatment reduced the size of pancreatic tumors in mice by an average of 80% and also significantly reduced the number of metastases by 87%, while treated animals lived 40% longer than untreated animals (controls) .

“The results indicate that this therapeutic approach could be a useful immunotherapy for pancreatic cancer, as well as other cancers, such as ovarian cancer, which remain difficult to treat,” notes Dr. Gravekamp, ​​Associate Professor of microbiology and immunology to Einstein and co-founder of Loki Therapeutics, who has licensed the underlying technology from the research center which plans to commercialize it for the benefit of patients.

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