Researchers develop promising therapy for malignancy of the pancreas

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Because it is most often diagnosed late, when it is already at a very advanced stage, malignancy of the pancreas is particularly difficult to treat. Researchers at the Albert Einstein University of Medicine have found a way to make tumors more detectable by the immune system. Their strategy is based on vaccination against ttanos, which everyone is supposed to receive from childhood. Tested on mice, their approach made it possible to reduce cancerous metastases by 87%.

Although relatively uncommon (it accounts for nearly 3% of cancers), pancreatic ductal adenocarcinoma, or malignancy of the pancras, is one more murderers. It remains without symptoms for a long time, which leads to late analysis in most cases. Boy treatment is therefore particularly difficult, since he silently sober creates numerous metastases (in the liver, abdomen and lungs). The tumors are also weakly immunogenic and are immunosuppressive, preventing the activation of P lymphocytes.

The problem is that pancreatic tumors are not foreign enough to attract the attention of the immune system and can usually suppress immune responses that learn to produce, explains Claudia Gravekamp, ​​associate professor of microbiology and immunology and co-author of the study presenting this new therapy. One strategy offered consists of making pancreatic tumors more vulnerable to the body’s immune defenses and in particular to T lymphocytes specific to ttanos, assuming that everyone is vaccinated against this disease.

Infect tumors with the ttanos

Many malignancies are now treated by immunotherapy, a strategy that involves helping the immune system identify and destroy tumor cells. Vaccines, cytokines, or antibodies are used to wake up the immune system. However, this approach does not work in the case of pancreatic malignancy: these tumor cells are immunosuppressive, which means that they develop mechanisms that could completely escape the immune system. In particular, they stop expressing certain immunogenic antigens and produce proteins that inactivate the immune defences.

Ttanus is a disease resulting from the infection of a wound or injury by spores of a bacterium Clostridium tetani . A vaccination, based on tetanus toxoid, provides lifelong protection against this disease, the problem of having received three dosages during childhood (before the age of one year) and of having carried out its booster dosages. Vaccinated individuals develop a strong immune response if they are exposed to the tetanus toxin, ttanaspamine, during their lifetime.

Gravekamp and his colleagues have therefore european union aims to infect pancreatic cancer cells with bacteria that release tetanus toxin, in a simple way to elicit the same immune response. To do this, they began by vaccinating mouse models of pancreatic malignancy against ttanos (using the same anti-tetanus vaccine as that used in humans). They then integrated the gene encoding put the tannic toxin of bacteria of the type Listeria monocytogenes usually non-pathogenic, this species causes listriosis. These bacteria have been chosen for their great abilities to infect cells and spread in tissues.

Finally, to infect tumors with a tannic toxin, they injected the genetically modified bacteria directly into the abdomen of mice bearing tumors and previously vaccinated. As soon as the bacteria infect the tumor cells, they produce tetanus toxin, triggering a specialized immune response. A toxin activated the Ttanus-specific memory capital lymphocytes and incited them to attack the infected tumor cells.

The size and the number of tumors reduced sober 80%

Researchers have taken advantage of the fact that pancratic tumors are immunosuppressive. Thus, only the bacteria present in the tumor microenvironment survive long enough to be able to infect the tumor cells; healthy cells are not infected: bacteria are very quickly and easily destroyed by the immune system. The mice showed no significant side effects to the treatment.

The team clarified that a response of the cells Big ta testosterone levels is reinforced by the addition of sober low dosages sober gemcitabine a drug that reduces immune deficiency, used in chemotherapy treatment for many cancers. This new therapeutic strategy showed very promising results: the treatment reduced the size of pancreatic tumors in mice by 87% on average and also reduced the number of metastases, while characteristic animals lived % longer than unqualified animals, report the researchers. human. In the event of success, this therapeutic approach could be a necessary immunotherapy for malignancy of the pancras, as well as for other types of malignancy, such as malignancy of the ovary or the brain, which also remain particularly difficult to treat.

Supply:BD Selvanesan et al., Technology Transitional Medication