Lead author Dr. Claudia Gravekamp, associate professor of microbiology and immunology at the Albert Einstein Cancer Center explains that pancreatic tumors are not “foreign” enough to attract the attention of the immune system and may even inhibit immune responses. The new therapy developed by his team makes immunologically “cold” tumors “hot” enough for the immune system to spot, attack and destroy them.
Take advantage of the widespread tetanus vaccination
The research : the New York team exploits the fact that virtually all people are vaccinated in childhood once morest tetanus, a serious illness caused by a toxic protein secreted by Clostridium bacteria. Thanks to their tetanus-specific memory T cells, which circulate for life in the bloodstream, vaccinated people will mount a strong immune response if they are subsequently exposed to the highly foreign tetanus toxin. The concept is to elicit a powerful and specific immune response once morest pancreatic cancer cells by pre-infecting them with bacteria that release tetanus toxin into the cells.
With the same vaccine used to vaccinate humans once morest tetanus, the researchers vaccinated pancreatic tumor model mice and then fused the gene that codes for tetanus toxin into non-pathogenic Listeria bacteria, which are very good at infecting cells and spread through the tissues. To infect and “tetanize” tumors, they injected the bacteria with their cargoes of tetanus genes.
Harnessing the immune response once morest a common bacterium: Listeria bacteria are easily killed by the immune system of humans and animals everywhere except in tumor areas. But while pancreatic tumors are very good at suppressing the immune system to protect themselves, only listeria bacteria present in tumor areas survive long enough to infect pancreatic tumor cells. Thus healthy cells are not infected! Once the Listeria bacteria infect the tumor cells, the tetanus toxin genes express the toxin protein inside the tumor cells, which triggers a strong immune response: in effect, the tetanus toxin activates the T cells memory specific to pre-existing tetanus, which induces, by CD4 T lymphocytes, the destruction of infected tumor cells.
Boost immunotherapy a little more: here, researchers are enhancing the T-cell response by adding low doses of gemcitabine (a chemotherapy drug that reduces immune suppression). In the end, this combined immunotherapy + chemotherapy treatment allows:
- to reduce, once more in mice, the size of pancreatic tumors by an average of 80%;
- significantly reduce the number of metastases by 87%;
- prolong survival by 40% in treated animals.
So a promising immunotherapy not only for pancreatic cancer but also for other types of cancer, such as ovarian cancer, which remain difficult to treat.
