Researchers harness immune system to fight pancreatic cancer

September 24, 2013

(Medical Xpress)—Pancreatic cancer ranks as the fourth-leading cause of cancer death in the United States, and is one of the most deadly forms of cancer, due to its resistance to standard treatments with chemotherapy and radiation therapy and frequently, its late stage at the time of diagnosis. A group of researchers led by the University of Pennsylvania's Perelman School of Medicine and Abramson Cancer Center, in collaboration with scientists from the University of Pittsburgh and University of Washington, published results of a clinical trial in which the standard chemotherapy drug for this disease, gemcitabine, was paired with an agonist CD40 antibody, resulting in substantial tumor regressions among some patients with advanced pancreatic cancer. By using a novel, real-time imaging approach to monitor tumor response to the immunotherapy, the team also found differences how primary and metastatic disease sites shrank. Their work appears online this month in Clinical Cancer Research.

"We're now using imaging to understand the treatment heterogeneity that one can see in immunotherapy – not all tumors within a patient's body react the same way, even in the face of powerful treatments, and now we have a way to follow these unique treatment responses in patients in real-time," said lead author Gregory Beatty, MD, PhD, an assistant professor in the division of Hematology/Oncology in the Abramson Cancer Center.

The report builds on preliminary results of findings in both humans and mice published in Science in 2011. The new approach exploits an in the microenvironment of the patient's primary tumor by targeting an immune cell surface molecule CD40 to turn a type of white blood cell known as macrophages against the tumor by causing them to attack the stroma, the fibrotic supporting tissue of the tumor that acts as a defensive barrier to standard therapies. The treatment ate away at this , ultimately causing substantial shrinkage of some primary tumors, and affecting the metabolic activity of both primary and metastatic lesions. Of 21 patients treated with the drug combination, five patients who received at least one treatment course developed a partial response, defined as a decrease in tumor size of at least 30 percent.

The study new also measured the effectiveness of applying a new approach to FDG/PET-CT imaging, to reveal the metabolic responses of individual tumors. FDG/PET-CT uses a radioactive glucose tracer to pinpoint glucose uptake within tumors, revealing the places where cells are metabolically active. Typically physicians and radiologists report only the maximum uptake of glucose within a tumor using this imaging technique; however, the new study showed that glucose metabolism can be quantified within individual tumors or within organs, and throughout the entire body, to provide a measure of total tumor burden.

The team found that while primary tumors seemed to respond more or less uniformly with each treatment cycle, tumors varied in their reactions to treatment. "We incorporated imaging as early as two weeks after the first dose of treatment, and we're able to see changes and responses in terms of glucose metabolism even at this early time point in treatment, which predicted how well patients would respond two months later," Beatty says. The team hopes to apply the use of FDG/PET-CT to monitoring treatment responses during other immune-based therapies in pancreas cancer.

Determining the reasons for these varying responses will be an important next step in this work. The unique imaging approach, Beatty notes, is revealing new insight into the biology of pancreas cancer and its treatment resistance. This allows the research team to expedite progress through a unique model that moves quickly back and forth between the lab and the clinic: "We're taking it back to the bench and at the same time, applying it at the bedside with additional clinical trials."

The most commonly observed side effect of the treatment was cytokine release syndrome, typically manifested as chills and rigors. One patient with a previous history of vascular disease experienced a stroke shortly after starting therapy.

Explore further: PET predicts early response to treatment for head and neck cancer patients

More information: clincancerres.aacrjournals.org … 432.CCR-13-1320.long

Related Stories

PET predicts early response to treatment for head and neck cancer patients

October 1, 2012
Determining the optimal treatment course and predicting outcomes may get easier in the future for patients with head and neck sqaumous cell carcinomas (HNSCCs) with the use of an investigational imaging agent. Research published ...

Combining CT, FDG-PET provides more accurate treatments for head and neck cancer patients

April 29, 2011
Combining computerized tomography (CT) with fluorodeoxyglucose positron emission tomography (FDG-PET) images results in significantly more defined tumor outlines and potentially different treatment options in head and neck ...

Promising drug prevents cancer cells from shutting down immune system

June 4, 2013
(Medical Xpress)—An investigational drug that targets the immune system's ability to fight cancer is showing promising results in Yale Cancer Center (YCC) patients with a variety of advanced or metastatic forms of the disease. ...

Depletion of 'traitor' immune cells slows cancer growth in mice

September 16, 2013
When a person has cancer, some of the cells in his or her body have changed and are growing uncontrollably. Most cancer drugs try to treat the disease by killing those fast-growing cells, but another approach called immunotherapy ...

Doctors look at treating specific types of pediatric cancer with viral therapy

September 10, 2013
(Medical Xpress)—Parents do everything they can to protect their children against all of the nasty germs floating around classrooms across the country this time of year. Doctors and researchers at Nationwide Children's ...

Recommended for you

Physical activity could combat fatigue, cognitive decline in cancer survivors

July 25, 2017
A new study indicates that cancer patients and survivors have a ready weapon against fatigue and "chemo brain": a brisk walk.

Breaking the genetic resistance of lung cancer and melanoma

July 25, 2017
Researchers from Monash University and the Memorial Sloan Kettering Cancer Center (MSKCC, New York) have discovered why some cancers – particularly lung cancer and melanoma – are able to quickly develop deadly resistance ...

Anti-cancer chemotherapeutic agent inhibits glioblastoma growth and radiation resistance

July 24, 2017
Glioblastoma is a primary brain tumor with dismal survival rates, even after treatment with surgery, chemotherapy and radiation. A small subpopulation of tumor cells—glioma stem cells—is responsible for glioblastoma's ...

New therapeutic approach for difficult-to-treat subtype of ovarian cancer identified

July 24, 2017
A potential new therapeutic strategy for a difficult-to-treat form of ovarian cancer has been discovered by Wistar scientists. The findings were published online in Nature Cell Biology.

Immune cells the missing ingredient in new bladder cancer treatment

July 24, 2017
New research offers a possible explanation for why a new type of cancer treatment hasn't been working as expected against bladder cancer.

No dye: Cancer patients' gray hair darkened on immune drugs

July 21, 2017
Cancer patients' gray hair unexpectedly turned youthfully dark while taking novel drugs, and it has doctors scratching their heads.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.