A UK team has discovered how to undermine a protective wall that pancreatic cancer tumors maintain around themselves, thus enabling the body's own immune cells - which they boosted with an antibody - to enter and attack cancer cells.
In initial tests carried out at the Cancer Research UK Cambridge Institute, based at the University of Cambridge, the combined treatment almost completely eliminated cancer cells in 1 week.
Study leader Prof. Doug Fearon, who heads the Tumour Immunology Laboratory at the Institute, says:
"By enabling the body to use its own defences to attack cancer, this approach has the potential to greatly improve treatment of solid tumors."
He and his colleagues report their findings in the latest print issue of the Proceedings of the National Academy of Sciences, PNAS.
First reported immunotherapy success in pancreatic cancer
Pancreatic cancer is a disease where symptoms rarely show in the early stages, so it is usually only diagnosed once it has spread to other parts of the body, and prognosis is poor.
According to the National Cancer Institute, for the year 2013, 45,220 Americans will have discovered they have pancreatic cancer, and 38,460 will have died of the disease. In the UK, where survival rates are equally poor, it is the fifth most common cause of cancer-related deaths. Worldwide, it is the eighth.
This new study from Prof. Fearon and colleagues is the first to report success with "immunotherapy" in pancreatic cancer.
Immunotherapy is a promising new field of cancer treatment that focuses on stimulating the patient's own immune system to attack the cancer.
It has shown particular promise in cancers with solid tumors, but patients with pancreatic cancer have not responded to this approach. This could be because, as in some other solid tumors, pancreatic cancer protects itself with a barrier.
Drug breaks down protective barrier surrounding tumors
The immune system has some inbuilt capacity to deal with cancer cells. Part of this is the T cell, which can recognize and attack cancer cells. But in the case of pancreatic cancer, the cancer cells have developed a way to shield themselves from T cells.
Working with a mouse model of human pancreatic cancer, Prof. Fearon and colleagues discovered that this shield or barrier takes the form of a chemokine protein, CXCL12, that coats the cancer cells and keeps the T cells away.
The protein is made by a specialized kind of connective tissue cell, called a carcinoma-associated fibroblast, or CAF.
Prof. Fearon explains:
"We observed that T cells were absent from the part of the tumor containing the cancer cells that were coated with chemokine, and the principal source of the chemokine was the CAFs."
He and his colleagues also found that removing CAFs from the pancreatic cancer appeared to allow the immune system to control the growth of the tumor.
They went on to find a way to remove the protective effect of the shield by using a drug that stops the T cells from interacting with the protein CXCL12.
The drug is AMD3100, also known as Plerixafor, which blocks the T cells' receptor for the cancer-shielding protein CXCL12.
And when they used Plerixafor with anti-PD-L1, an immunotherapeutic antibody that boosts T cell activity, the number of cancer cells and the size of the tumor shrank significantly.
After 1 week of combination treatment, the shrunken tumor contained only premalignant cells and inflammatory cells.
Support and funds for the study came from Cancer Research UK, GlaxoSmithKline, the Medical Research Council, Addenbrooke's Charitable Trust, the Ludwig Institute for Cancer Research, and the Anthony Cerami and Anne Dunne Foundation for World Health.
In another study published recently in the journal Clinical Cancer Research, a team from the US showed how a combination of immunotherapy and gene therapy could lead to an effective treatment for breast cancer that has spread to the brain.