Capturing cancer: a powerful new technique for early diagnosis

Despite impressive medical strides, cancer remains a leading killer and overwhelming burden to healthcare systems, causing well over a half million fatalities per year with a projected cost of $174 billion by 2020, according to the National Cancer Institute. Reducing the human and economic toll will require diagnosis and intervention at early stages of illness, when the best prognosis for a cure exists.

In recent years, aggressive research and substantial financial investments have been directed at discovering pre-symptomatic indicators of cancer, known as biomarkers. But as lead author Phillip Stafford and his colleagues at Arizona State University’s Biodesign Institute emphasize in a new study, the quest for cancer biomarkers has been stymied by a number of factors.

In research appearing in today’s issue of the journal Proceedings of the National Academy of Science, Stafford and his team describe an innovative technique for early disease detection, which they call immunosignaturing.

“For years we’ve seen remarkable results from immunosignatures, but introducing the technology to the scientific community has required a lot of patience,” Stafford says.

Stafford is a researcher in Biodesign’s Center for Innovations in Medicine which is co-directed by Stephen Albert Johnston, who is also one of the new study’s co-authors.

To date, only a handful of cancer biomarkers have received FDA approval for clinical use and even approved biomarkers are sometimes of limited utility. The problems are numerous. The body’s immune response to cancer is complex, heterogeneous and differs from patient to patient, as well as depending on depending on cancer type and stage.

Individual biomarkers often lack the sensitivity and resolution for positive diagnosis and diagnostic molecules, including RNA, DNA, proteins or peptides are often present in vanishingly slight amounts, after diluting in the bloodstream, making accurate detection especially challenging. Vast research efforts notwithstanding, efforts to establish better pre-symptomatic beacons of disease have been disappointing.

Immunosignatures take a different approach. Rather than using a reductionist biomarker paradigm, it relies on a multiplexed system in which the entire population of antibodies circulating in blood at a given time is profiled.

The technique relies on a microarray consisting of thousands of random sequence peptides, imprinted on a glass slide. (The peptides used are 20 unit amino acid chains, randomly composed.)

When a tiny droplet of blood, (less than a microliter is needed), is spread across the microarray, antibodies in the blood selectively bind with individual peptides, forming a portrait of immune activity—an immunosignature.

Because the peptide sequences are random and not related to any naturally occurring disease antigens, the authors refer to immunosignatures as “disease agnostic,” which means that a single platform is potentially applicable to multiple disease types. This is a substantial improvement over highly specific bioassays that can only test for a single biomarker antibody, often with substantial misidentification or inadequate sensitivity.