Medical Device Link.

Originally Published IVD Technology July 2003

INDUSTRY NEWS

Jennifer Zakroff

The spotlight still shines brightly on proteomic microarrays and their gradual emergence into the realm of clinical diagnostics. The media, researchers, and many professional IVD societies, including the Clinical Ligand Assay Society (Wayne, MI) whose annual meeting devoted much time to clinical applications of arrays, view this technology as a key to a virtual treasure trove of information. However the IVD manufacturing industry is not yet sold.

Industry leaders such as Celera (Alameda, CA), Abbott (Abbott Park, IL), and Roche (Basel, Switzerland), and mid-sized companies including Affymetrix (Santa Clara, CA) and Ciphergen (Fremont, CA) are developing the technology as a research tool with plans to broach the clinical market. Yet IVD industry consensus is that, although arrays are a valuable tool for finding genetic markers, this technology is still far from ready to make waves in the marketplace. The use of DNA arrays in clinical diagnostics may be a long way off, but the technology has recently achieved a remarkable victory.

Researchers at the Wistar Institute (Philadelpha) have used customized DNA arrays to examine the activity of 4500 genes suspected to be linked to a leukemic form of lymphoma known as Sezary Syndrome (SS). Full study results have been written up in a report in the June 2003 issue of the Journal of Experimental Medicine titled, “Classification and Prediction of Survival in Patients with the Leukemic Phase of Cutaneous T Cell Lymphoma.” 

In the study, scientists compared blood samples from 45 cancer patients with those from 20 controls and identified 385 genes that were either over- or underactive. A panel of only 8 of the 385 genes enabled investigators to accurately diagnose SS in patients with tumor burdens as low as 5% of their circulating blood cells. A 10-gene panel was powerful enough to identify a class of cancer patients who will succumb to their disease within six months, regardless of their tumor burden. 

Thus, not only did the microarrays offer the ability to predict patient response to therapies, but they also pointed to targets for pharmacological intervention. The fact that this study is geared toward expressed genes also raises the possibility of identifying protein targets for immunoassay development and for development of therapeutic antibodies.

“Clearly, this work is a milestone in the path toward using DNA arrays for diagnostics,” remarks Richard Root, principal scientist and manager of laboratory systems at Roche Diagnostics (Indianapolis). “I do see this work as a very important development. I also think that it is too early to be predicting any shifts in R&D directions in the near future.” 

Although this study was successful, more research must be done before its clinical implications are fully developed. The authors mention that studies with larger groups of patients and different disease states will be important. In addition, both the cost-effectiveness of DNA array technology and its suitability for clinical applications will have to be further verified before the IVD manufacturing industry takes hold of microarrays for distribution to the clinical market. 

As to market acceptance, the IVD systems that read microarrays must be honed and improved. “A great deal depends on engineering of automated, validated systems for carrying out the chemistry and analysis before [the widespread use of microarray technology in clinical IVDs] can be an attainable goal. I personally do not think it likely that much effort will be expended toward that until research efforts yield other disease states to the list of those identifiable by DNA arrays. Right now, as far as I can tell, DNA array work in the industry is primarily focused on identifying protein targets for diagnostics,” says Root.

The Wistar study is available for purchase on-line at http://www.jem.org. 

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