Researchers have used overall immunity against tetanus to deliver a targeted infection to pancreatic cancer cells, which then prompts an immune response against cancer cells.
Pancreatic cancer is bad news; patients who have it are difficult to treat or cure. The American Cancer Society puts the 5-year relative survival rate for pancreatic cancer at 11 percent.
Now, a new strategy formulated by scientists at Albert Einstein College of Medicine in New York has made pancreatic tumours detectable by the immune systems of mice and exposed to immune attack, reducing cancer metastases by 87 percent.
“Today’s checkpoint inhibitor drugs work well against some types of cancer but only rarely help people with pancreatic cancer,” said Claudia Gravekamp, PhD, corresponding author of the paper and associate professor of microbiology & immunology and a member of the National Cancer Institute-designated Albert Einstein Cancer Center.
“The problem is that pancreatic tumours aren’t sufficiently ‘foreign’ to attract the immune system’s attention and can usually suppress whatever immune responses do occur. Essentially, our new therapy makes immunologically ‘cold’ tumours hot enough for the immune system to attack and destroy them.”
The authors write that they “have solicited the help of Listeria monocytogenes to deliver highly immunogenic tetanus toxoid proteins directly into tumour cells. This delivery elicits an immune response, activating tetanus toxoid–specific memory T cells to kill tumour cells in mice.”
With the help of Listeria bacteria to deliver inactivated forms of tetanus toxins to pancreatic tumour cells, the researchers were able to bring out an immune response, activating cancer killing immune response T cells.
Making use of the tetanus vaccine
The researchers are acting on the fact that almost everybody is vaccinated in childhood against tetanus, an infection caused by bacteria called Clostridium tetani. Likewise, because of the tetanus shot, almost everybody has tetanus-specific memory T cells in their bloodstream.
This allows their immune system to fight against the tetanus toxin if they are exposed later in life. The researchers, banking on this immune response, infected pancreatic cancer cells with bacteria that deliver tetanus toxin into the cells.
How did they do it? The scientists vaccinated mice (that were programmed to develop human pancreatic tumours) with the same tetanus vaccine given to people. Then they injected the mice with Listeria bacteria enhanced with tetanus.
“The Listeria bacteria are quite weak and are readily killed off by the immune systems of people and animals—everywhere, that is, except in tumour areas,” Gravekamp said.
“Our treatment strategy actually takes advantage of the fact that pancreatic tumours are so good at suppressing the immune system to protect themselves. This means that only those Listeria bacteria in the tumour region survive long enough to infect pancreatic tumour cells and that healthy cells don’t become infected.”
The Listeria bacteria infecting tumour cells provoke a strong immune response. The tetanus toxin activates pre-existing tetanus-specific memory T cells, causing CD4 T cells to attack and kill the infected tumour cells.
The researchers helped the T cells’ response with the addition of low doses of gemcitabine, a chemotherapy drug that reduces immune suppression.
Thanks to the Listeria treatment, the size of pancreatic tumours in mice shrank by an average of 80 percent and also significantly lowered the number of metastases by 87 percent.
The mice who received tetanus toxoid protein via Listeria also lived 40 percent longer than the untreated control mice.
“The findings indicate that this treatment approach could be a useful immunotherapy for pancreatic cancer as well as other types of cancer, such as ovarian cancer, that remain difficult to treat,” said Gravekamp.