Skip Content

New potential immune therapy for pancreatic cancer discovered

25 March 2011

Researchers at the University of Pennsylvania have discovered a new way of treating pancreatic cancer that uses the body’s immune system to destroy the ‘scaffolding’ around the tumour.

Researchers at the University of Pennsylvania have discovered a new way of treating pancreatic cancer that uses the body’s  immune system to destroy the ‘scaffolding’ around the tumour.

The strategy has been tested in a small cohort of patients with advanced pancreatic cancer, resulting in several patients’ tumours shrinking substantially.  

The researchers treated 21 patients with standard gemcitabine chemotherapy in conjunction with an experimental antibody manufactured by Pfizer Corporation. They hoped that the antibodies would bind to a specific receptor on the cell surface called CD40 and kickstart the immune system’s key players  -  T-cells -  into attacking the tumour. 

The treatment appeared to work; some patients' tumours shrank significantly and the majority of tumours lost metabolic activity after the treatment, although all of the responding patients eventually relapsed. However, when the researchers examined the post-treatment tumour samples,  to their surprise they found no  T-cells.  Instead, they saw an abundance of another white blood cell known as macrophages – more basic cells which form part of the body’s defence mechanism against viruses and bacteria.

Pancreatic tumours are known to secrete chemical signals that attract then force macrophages to protect the tumour, but closer inspection showed that these macrophages were instead attacking what is known as the stroma, the supporting scar tissue around the tumour.  

Although the stroma does not itself include cancer cells, it can account for the bulk of a tumour and serves as a dense, fibrotic, and hostile barrier that prevents chemotherapy drugs from reaching cancer cells.

"The tumor is still calling in macrophages, but now we've used the CD40 receptor to re-educate those macrophages to attack - not promote - the tumor," said Robert Vonderheide, associate professor of Medicine at the University’s Abramson Family Cancer Research Institute. "It is something of a Trojan horse approach."

"Until this research, we thought the immune system needed to attack the cancer directly in order to be effective," said Vonderheide.  "Now we know that isn't necessarily so. Attacking the dense tissues surrounding the cancer is another approach, similar to attacking a brick wall by dissolving the mortar in the wall. Ultimately, the immune system was able to eat away at this tissue surrounding the cancer, and the tumours fell apart as a result of that assault. These results provide fresh insight to build new immune therapies for cancer."

The research has been published in the journal Science.

< Back