Immune signature in blood could enable earlier detection of pancreatic cancer


Less than one in ten cases of pancreatic cancer in the U.S. are diagnosed at the local stage. And the relative survival rate — around 6 percent at five years — is by far the worst among major cancers. The OHSU Knight Cancer Institute and the Swedish biotech firm Immunovia AG recently announced a collaboration to develop blood tests that could enable earlier diagnosis of pancreatic cancer.

Immunovia’s technology uses a microarray with recombinant antibodies as probes to detect a specific set of proteins in blood, many of them involved in immune regulation. It produces a snapshot of immune activity in a patient at the time of the blood draw that reflects both the systemic response to cancer and tumor-secreted factors, in the words of Immunovia founder Carl Borrebaeck and colleagues at Lund University and Karolinska Institute.

An early version of the microarray targeting 25 biomarkers — including cytokines, complement proteins and enzymes — distinguished pancreatic cancer samples from pancreatitis and healthy control samples with a sensitivity of 73 percent and specificity of 75 percent, Borrebaeck and co-authors reported in a 2012 paper in the journal Cancer Research.

The figure above is a heat map from the 2012 paper comparing serum levels of 20 proteins in a group composed of 34 people with pancreatic cancer and 30 serving as healthy controls. The colors indicate the relative expression levels of the proteins (labeled on the right) in each of the 64 people: red for upregulated, green for downregulated, and black for equal levels. In people with pancreatic cancer, nearly all of the proteins are upregulated. Two proteins, C1q and properdin, are downregulated.

Immunovia has continued to refine the protein analysis platform since 2012, adjusting the set of antibody probes to improve performance. Knight Cancer scientists will help confirm the biomarkers targeted in the microarray by running a retrospective study on blood samples collected from consenting patients with pancreatic ductal adenocarcinomas.

The company says it sought the collaboration with the OHSU Knight Cancer Institute because of its commitment to early detection of cancer — but also the depth of data collected on patient samples at OHSU’s Brenden-Colson Center for Pancreatic Care (co-directed by Brett C. Sheppard, M.D., and Rosalie C. Sears, Ph.D.), and the expertise of its molecular diagnostics laboratories (headed by Christopher Corless, M.D., Ph.D.)

The clinical validation study will cover about 600 samples, including those from patients with different stages of pancreatic cancer, matched controls and patients with chronic pancreatitis, the news release said. If all goes well, the OHSU Knight Diagnostic Laboratories will validate the serum biomarker test for clinical application. And this is just the beginning.

Knight Cancer and Immunovia plan to work on tests for other cancers using the company’s protein microarray and analysis technology, which has the potential to become a valuable part of the institute’s precision early detection research program.

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Identification of Serum Biomarker Signatures Associated with Pancreatic Cancer by Christer Wingren, Anna Sandström, Ralf Segersvärd, Anders Carlsson, Roland Andersson, Matthias Löhr, and Carl A. K. Borrebaeck. Cancer Research (2012)