ABBOTT PARK, Ill.—Abbott will collaborate with Merck toevaluate the use of a fluorescence in-situhybridization (FISH)-based companion diagnostic test to aid in the developmentof a Merck investigational cancer therapy.
FISH-based companion diagnostic tests are designed toidentify specific DNA sequences to help guide physicians in determining whichpatients are more or less likely to benefit from a particular therapy. FISHtechnology has a variety of uses, an Abbott spokesperson points out. It canidentify whether too many, or too few, copies of a particular gene are presentor whether certain genes have rearrangements that play an active role indisease progression.
"The use of FISH to determine genomic status and the link totherapeutic outcome in oncology is one of the fastest-growing applications. Inthis instance, a FISH assay will be developed to examine copy number of theTP53 gene," she adds.
The Abbott FISH assay will be evaluated in clinical trialsto help identify patients more likely to respond favorably to Merck's as-yetunidentified investigational cancer therapy.
Merck evaluated number of potential partners and Abbott waschosen as a partner to develop this companion diagnostic test.
"We have proven capabilities to take a product through theregulatory process, manufacturing, distribution and implementation in aclinical lab setting," the Abbott spokesperson says.
Merck will be responsible for establishing the clinicaltrial sites with regard to all aspects of patient recruitment and therapyadministration. Abbott Molecular will work with Merck to select the FISHtesting labs, and then Abbott will provide assay training and monitor thelaboratory sites.
"Our goal through this collaboration, and others like it, isto ensure that the right medicine gets to the right patient," says StaffordO'Kelly, head of Abbott's molecular diagnostics business. "As one of the earlypioneers in companion diagnostics, we believe that linking genetic testing withdrug development at the earliest stages can increase the effectiveness andpredictability of medicines and help physicians make more informed treatmentdecisions."
Abbott's portfolio of companion diagnostic tests includesthe PathVysion HER-2 DNA Probe Kit, which represents one of the first examplesof innovations in the field of personalized medicine. The test is approved foruse in selecting breast cancer patients for whom Herceptin (trastuzumab)therapy is being considered. In addition, Abbott's Vysis ALK Break Apart FISHProbe kit was approved in 2011 for use in identifying non-small cell lungcancer patients for Pfizer's XALKORI (crizotinib) treatment in the UnitedStates, Canada, South Korea, Japan and a number of other markets. Globalcommercialization continues to progress as Xalkori and Vysis ALK receiveadditional individual country approvals, Abbott notes.
"Our collaboration with GSK was expanded in November 2011.The existing agreements focused on the development of PCR tests to screennon-small cell lung cancer and melanoma tumors for expression of the MAGE-A3antigen. Under the expanded agreement, Abbott will develop a PCR test for useon the Abbott m2000rt instrument, to screen non-small cell lung cancer tumorsfor the expression of the PRAME antigen. PRAME is a preferentially expressedantigen of melanoma that is expressed in 69 percent of non-small cell lungcancer cases, as well as in a wide variety of cancer types, including melanoma,breast, ovarian and bladder cancer, with limited expression in normal cells,"the spokesperson tells ddn.
Abbott Molecular is a leader in molecular diagnostics—theanalysis of DNA and RNA at the molecular level. Abbott Molecular's tests canalso detect subtle but key changes in patients' genes and chromosomes and havethe potential for earlier detection or diagnosis, provide information relevantto the selection of appropriate therapies, and may improve monitoring ofdisease progression.
In an unrelated development, Abbott will collaborate withGenetics Laboratory Inc. (GenLab) on the development of a molecular diagnostictest that will be designed to rapidly detect microorganisms that cause orthopedicinfections. Under terms of the agreement, Abbott, in conjunction with GenLab,will develop and commercialize the new assay for use on the PLEX-ID automatedmicrobial identification system. In the United States, PLEX-ID is currentlyintended only for non-diagnostic use, but assays are now being developed forfuture clinical diagnostic uses.
PLEX-ID has the ability to rapidly identify a broad varietyof microorganisms. The system is capable of generating results within five tosix hours in contrast to other methods, which may take several days or longerfor positive identification.
"Bacteria, particularly antibiotic-resistant species such asMRSA, are very dangerous in orthopedic patients because the bacterial coloniesattach to the artificial surfaces of the implants," says Dr. Gerhard Maale, anorthopedic oncologic surgeon and an expert in orthopedic infections in theDallas-Ft. Worth area.
Maale will also serve as the medical director for theAbbott-GenLab collaboration.
"A molecular diagnostic test designed to detectmicroorganisms that cause orthopedic infections, running on the PLEX-ID, couldhave the ability to determine which pathogens are responsible for an infectionwhile assessing the genetic composition and potentially antibiotic resistance,"Maale says. "This could be a major step forward in diagnosing and treatingserious infections in artificial joint recipients, with the potential toprovide important information to physicians that they could use to savetreatment costs and improve the quality of life for these patients."
According to the New England Journal of Medicine, about 800,000 knee and hip replacement proceduresare performed annually in the United States, and complications related toinfections occur in approximately 2 percent of those procedures. In addition,more than 70,000 joint revisions are performed annually in the United States,with greater than 15 percent of hip and 25 percent of knee revisions caused byinfections. Revisions are often more expensive than the original procedure.
FISH: Navigatingthe waters of personalized medicine
PRETREATMENT: Cellsor tissue are placed on a slide and treated (fixed) to stabilize cellularstructures. Chemical and enzymatic procedures are employed to remove membranes,and cytoplasmic proteins that prevent access to the cells' DNA.
DENATURATION: CellDNA is exposed to high temperature in order to open the DNA, making itaccessible to fluorescent-labeled probe DNA.
HYBRIDIZATION: Probeis added to the sample and allowed to combine with complementary sequence ofthe target DNA.
WASHING: Excessprobe is removed post-hybridization, and a counterstain is applied to visualizethe individual cells and nuclei.
FISH can utilize more than one fluorescent label at one timeto be able to detect multiple genes (or gene loci) in a single hybridization.Colors are counted or enumerated to determine the gene status, amplification,deletion and translocation.