SCHOTT solutions no. 1/2011 > Biotechnology

In customized cancer therapy, each individual patient receives just the right therapy with the help of biomarkers to improve the survival rate and reduce side effects. The use of biochips based on nitrocellulose-coated microscope slides represents a powerful tool for identifying and classifying biomarkers. Photo: SCHOTT + CAPMM/Montage: dw

On the Way to Customized Cancer Therapy

SCHOTT Nexterion® nitrocellulose-coated glass slides play a key role in developing new diagnostic tests for the personalized treatment of cancer.

Virginia Espina & Claudius Müller

Most people know a friend or family member who has been diagnosed with cancer. Although great strides are being made in cancer therapy, too often cancer treatment fails or causes side effects with no therapeutic benefit. Scientists and treating physicians agree that the next revolution in cancer treatment will be individualized therapy. Individualized therapy uses characteristic biological indicators (biomarkers) to guide the right therapy to the right patient. The hope is that this approach will improve patient survival and have reduced side effects. A powerful tool for identifying and classifying such biomarkers is the use of biochips based on nitrocellulose-coated glass microscope slides. Clinical research trials currently recruiting patients are using Nexterion® nitrocellulose-coated slides to map the inner control circuitry of a patient’s cancer cells. The map highlights the regions of the cancer cell circuitry that may be causing the cancer to grow or invade and spread in the patient’s body. The diagnostic report is similar to a GPS map – showing the cell pathways instead of roads, with a highlighted route, which is the target for new cancer treatments. This information is used by the treating physician, under the research protocol, to select the best therapy for the patient.
The Center for Applied Proteomics and Molecular Medicine, U.S.A, creates and patents new technologies for translational research, and applies these technologies to individualized therapy, early disease ­detecttion, and chemoprevention. Photo: CAPMM
”It is imperative that the nitrocellulose slides used in this test be of the highest quality because the patient specimen is irreplaceable and a treatment decision may be based on the results,” explains Dr. Lance Liotta, Co-director of the Center for Applied Proteomics and Molecular Medicine (CAPMM) at George Mason University in Manassas, Virginia. ”Nexterion® NC-C slides meet our requirements for high binding capacity, with good batch-to-batch reproducibility for our breast cancer clinical trial. A surface that has a high protein binding capacity is required because of the small number of cells obtained from a patient’s sample,” he adds.

„The companion diagnostic market is exploding”

The biochips printed on nitrocellulose-coated slides provide a way to measure many proteins from a patient’s sample in a single test. The biochips were previously used as a research tool, but have now moved to use in research clinical trials with clinical grade sensitivity and precision. As the biochips made and used by George Mason University are classified as a “laboratory- developed test” (LDT), and do not currently require FDA approval, Nexterion® products are presently for research use only, not for use in diagnostic procedures.

The biochip platform is used for measuring cell signaling proteins in human samples from patients with melanoma, leukemia, breast, lung, or ovarian cancer. This test is also applied to eye disease, such as age-related macular degeneration, a leading cause of blindness. Biochip data can be applied to complex clinical questions, such as determining which molecules, in which cells, are affected by the drug treatment, predicting treatment outcome in different patient populations, or comparing the effects of treatment on various tumor types.

“The companion diagnostic market is literally exploding now, and we can easily envision a future whereby any FDA approved therapy will require a biomarker measurement that is used to select the patients for the therapy. The use of nitrocellulose slides as the substrate of choice by which many of the biomarkers are measured may underpin most of these assays,” says Emanuel Petricoin, Co-director of the CAPMM.
Nitrocellulose coated slides must be of the highest quality because they are used for precious diagnostic samples from patients. For this reason, manufacturing at SCHOTT, the leading supplier of microarray glass substrates under the Nexterion® brand, must meet exceptionally high quality standards. Photo: CAPMM
One may wonder why nitrocellulose is essential for quality protein biochips. Firstly, nitrocellulose coatings have a high protein binding capacity that makes it possible to use samples with a very limited number of patient’s cells, such as a small needle biopsy. Secondly, nitrocellulose polymers cast on glass slides provide a uniform coating which is essential for maximizing the number of patient samples per slide. In addition, the nitrocellulose can be cast in various geometries, such as a large single pad or multiple small pads. Lastly, large batches of nitrocellulose-coated slides can be manufactured to provide the reproducibility required for clinical-grade assays. The CAPMM creates and patents new technologies for translational research, and applies these technologies to individualized therapy, early disease detection, and chemo­prevention. Investigators in the center have developed state of the art test methods for use in cancer research and clinical trials. The clinical trials are conducted in collaboration with local community hospitals and physicians. Technologies invented within the Center have been commercialized through George Mason University leading to two spin-out companies, Theranostics Health and Ceres Nanoscience. The Center is one of a growing number of labs around the world that rely on nitrocellulose-coated slides for clinical diagnostics. “The high-quality nitrocellulose slides provided by SCHOTT Nexterion® are an important part of the future of medical treatment, which is individualized for the patient and tailored to their disease. The concept of personalized therapy based on an individual patient’s molecular profile will hopefully provide clinicians with the information required to optimally treat each patient’s disease while minimizing side-effects,” concludes Dr. Liotta. <|