Research

Diagnostics

Scientists from the Center for Innovations in Medicine in the Biodesign Institute at Arizona State University have developed a comprehensive, microchip-based technology, called immunosignature diagnosis, which can rapidly and comprehensively measure an individual’s vaccine response, promising to take much of the initial guesswork out of predicting effective vaccines.

Johnston is driven by the quest to develop disruptive technology that could make health care more effective and affordable. Despite 17 percent of the U.S. GDP tied to health care costs and growing, the U.S. does not get as much value per dollar as other countries (spending the most per capita yet ranking last in efficiency). He believes innovative diagnostic technologies that could determine whether or not an individual would get sick before symptoms appear, as well as the early identification of microbial culprits of infections has high potential for transforming medicine.

“We developed the immunosignature technology primarily for early detection of disease, but realized it may have other applications,” said Johnston, who directs the Center for Innovations and Medicine at the Biodesign Institute  “In this work we demonstrate that it may also be useful for screening candidate vaccines.”

Currently, the effectiveness of vaccines is evaluated by looking for the presence a particular type of antibody from the vaccine-generated immune response or by extensive and complicated sets of analyses. The power of the immunosignature is that this effectiveness can be completed in one fell swoop, by using thousands of random molecules aligned on a microscope slide, like the transistors on a computer chip.

“We use an array of 10,000 short peptides, each one about twenty amino acids long, to generate a high degree of specificity and sensitivity for measuring both human, dog, and mouse infections and chronic and genetic diseases,” said Legutki, a faculty in CIM and lead author of the paper. “A subset of these peptides will stand out, based on an individual’s antibody repertoire, and provide a unique pattern, or signature for a given disease.”

An immunosignature for valley fever was established using the 10K-peptide microarray, a smaller diagnostic array was composed from relevant diagnostic peptides. This smaller, 96-peptide array was then tested for accuracy against the current immunodiffusion diagnostic standard.

The 10K-peptide array successfully distinguished valley fever from three other infections, with 98 percent accuracy. Impressively, the method was also able to classify false negative valley fever patients in a blinded test with 100 percent accuracy, easily outpacing existing immunodiffusion methods, which could only identify 28 percent of false negatives.

The smaller, 96-peptide diagnostic array showed less specificity than the 10K-peptide array in terms of identifying false negatives. The authors propose that the larger 10K-peptide array be used in initial screenings, followed by subarrays with reduced complements of carefully selected peptides, used for clinical diagnosis.

Immunosignaturing holds the promise for rapid, cost-effective and highly accurate diagnosis of valley fever. The versatile platform has the potential to separate valley fever patients from those afflicted with other bacterial or fungal infections. Making use of the same microarray, researchers can also identify false negatives with 100 percent accuracy.

Immunosignatures are also fostering Biodesign start-ups. HealthTell Inc., a spin-out company from Arizona State University’s Biodesign Institute, was selected as the Start-up of the Year at the 2012 Governor’s Celebration of Innovation this week.

HealthTell Inc. has raised $4 million in new funding over the past few months to help commercialize a new test for lung, breast, prostate and colorectal cancers.

 


Cancer vaccines

Cancer disrupts lives, killing more than 7 million people worldwide each year. It is the second leading cause of death in the U.S. with half a million deaths each year. Treatment costs have also soared, now accounting for about 10 percent of the total U.S. healthcare costs.

Bold, new strategies are needed, and this project epitomizes that thinking. We’re attempting to eradicate cancer through protective vaccination.  The goal is to develop a vaccine that would be administered to healthy people to prime their immune systems for the recognition and destruction of a tumor and other malfunctioning cells.  It could also serve as a therapeutic treatment for early stage cancers.  

Clearly, the most successful medical intervention in history was the introduction of vaccines.  To date, such an approach for cancer was limited by the unique nature of each individual’s cancer.  But, we believe we may have found a link between proteins produced by various cancers that will make a cancer vaccine possible.

It’s been well-established that cancers create foreign proteins that the immune system can recognize.  The first cancer target we are exploring is breast cancer. The idea is to demonstrate that, if we could pre-immunize an individual with a collection of proteins that effectively represent any foreign protein that a breast tumor would produce, the immune system would arm itself against breast cancer.  If the platform technology proves successful, it could be applied to other cancers.

The Biodesign Institute and the Mayo Clinic Arizona are collaborating on the exploration of this research frontier. This epic endeavor brings the informatics, genomics, proteomics and immunology fields together to eradicate cancer.

The development of conventional preventative vaccines figures among mankind's greatest scientific achievements. Such innovations were an effective means of dramatically reducing mortality from scourges such as viral polio myelitis, smallpox, and measles.  The vaccines for these diseases, along with the newer Human papilloma virus and Hepatitis B vaccines, all use part of the viral protein coat as a stimulant for the immune system’s recognition abilities.  The vaccination process educates the immune system to attack the invading organisms via recognition of foreign biomolecules.  

Cancers engender a much more subtle situation:  they are not truly foreign to the body.  Derived from the body’s own cells, tumor cells look very much like normal, healthy cells.  While the bacteria and viruses that invade the body are easily recognized as “non-self” and destroyed, the immune system has a difficult time differentiating between tumor cells and healthy cells.  This situation is further exacerbated by the cancer cell’s ability to hide from the immune system’s killer T cells.  In all human cells, pieces of proteins are routinely displayed on the surface to be inspected by killer T cells.  If the proteins are recognized as normal fragments that should be present in the cell, the T cell proceeds on its way.  If the peptide is unrecognized, or is out of place, the cell will be destroyed.  

The vaccine will take cell surface antigens—the proteins and sugars from the exteriors of cells—and use them to provoke an immune response in a person.  The cancer-related cell surface antigens are unique or are more abundant on cancer cells than on normal cells. These can act as markers for the body to recognize the dangerous cells.  The immune system will initiate a cascade of events that will ultimately form antibodies to the antigens.  This will allow the body to target cells with the antigens and destroy them before they can form tumors. This way, the dangerous cells can be eliminated without collateral damage to healthy cells.  

With success in cancer vaccine therapy, the technology can be used to produce a near-universal, prophylactic cancer vaccine and that will make cancer a disease of the past.

Project funded with support from:

Innovator Award, U.S. Department of Defense, Breast Cancer Research Program

W.M. Keck Foundation