Focus sheep antibody are used. In fact, the immunoglobulin solution used to coat the polystyrene can be used several times without any apparent reduction in the sensitivity of the assay. The monoclonal antibody NK2, which is crucial to the assay, can be produced in large amounts without any change in quality. "Finally," writes Sécher, "the assay is inexpensive . . . , lends itself to automation, and several hundred samples can be assayed by one person in a day." Sécher cautions that biological antiviral assays will still be needed, however, to detect any interferons
that do not possess the NK2 antigenic binding site, and to confirm biological activity in substances that give positive antigenic reactions but which nevertheless may not always be interferon. Sécher hopes to improve the sensitivity of the immunoradiometric assay still further by optimizing the conditions at low interferon concentrations. "In any case," writes Sécher, "the sensitivity of the assay can be further increased by prior concentration and purification of the interferon on à small NK2 affinity column."
New Cancer Marker Molecule found loitering on biological street corners where cancer is known to tread An analytical test called a tumorspecific glycoprotein assay may soon permit early detection of a wide range of cancers in the human body. "What we're dealing with is a glycoprotein isolated from the serum of cancer patients that appears to be associated with the process of malignancy," explained Eugene A. Davidson, who developed the assay along with one of his graduate students, Sally D. Bolmer. Davidson is chairman of the Department of Biological Chemistry at the Penn State College of Medicine, and Bolmer is now a postdoctoral associate in the Nutrition and Food Science Department at the Massachusetts Institute of Technology. The assay may one day be used for cancer management to determine the effectiveness of surgery or therapy, and for initial screening or confirmation of the presence of cancer. Food and Drug Administration (FDA) approval would be required before such a test procedure could be marketed, however. This will necessitate further testing and evaluation in the next few years. "There's nothing invasive as far as the patient is concerned, other than withdrawal of the blood sample," Davidson declared. "It's as routine as any other hospital analytical procedure could possibly be." In the assay, reagents are added to the sample, and the concentration of marker glycoprot e i n ' s then determined by immunoassay. Warner-Lambert Company, licensee for the assay, has not yet determined whether the procedure will be a
radioimmunoassay (RIA) or a nonisotopic immunoassay. Warner-Lambert has been licensed to develop and market the new test, subject to FDA approval. Penn State was represented by the prestigious Research Corporation of New York in its search for a licensee for the new clinical test developed in its laboratories. Research Corporation accepts assignment of discoveries that originate at nonprofit institutions and appear patentable, useful, and marketable, and seeks patent protection and licensing on behalf of the university or other organization. Royalties from successfully licensed inventions are then distributed between the institution, the inventor, and Research Corporation, as specified by prior agreement. Research Corporation's share of any royalties received is used, in accordance with the nonprofit organization's charter, to support invention administration and research grants. Cancer test development began in the early 1970s, as cancer researchers began to identify certain antigens and enzymes—called markers—that were prevalent in cancer patients. A number of other tests are presently available. The best-known tumor marker, and the only one that has so far obtained FDA marketing approval, according to a recent article in Science (1981,211, 909-10), is carcino-embryonic antigen, which is associated with gastrointestinal tract cancer. Another well-known marker is alpha-fetoprotein, associated with liver, testicular, and gastric cancers. The new marker
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discovered by Davidson and Bolmer, however, appears to be applicable to a broader range of cancers than any previously discovered. According to Davidson, "So far we've found it in every solid and soft tumor tissue we've examined: mammary cancer, lung cancer, colon cancer, Hodgkin's disease, sarcomas, lymphomas, pancreatic cancers, prostate, rectal, etc." Davidson and Bolmer found in their study that the assay correctly indicated the presence of cancer in nearly 96% of the cases. "The levels in normal individuals are very, very low, and our false positives are also very low," Davidson explained. The molecule being assayed is a unique sialoglycoprotein not previously identified. Proteins may be divided into two major classes: simple and conjugated. Simple proteins yield only amino acids on hydrolysis, whereas conjugated proteins yield not only amino acids, but also other organic and inorganic components originating in covalently bound prosthetic groups. The glycoproteins are conjugated proteins that contain carbohydrate groups attached covalently to the polypeptide chain, and sialoglycoproteins also contain sialic acid residues attached to the carbohydrates. The just-discovered sialoglycoprotein marker is not necessarily an exclusive product of the tumor cell itself. Several possibilities exist in which that would not be the case. For example, it could be a molecule that is present on all cells, but only shed in the presence of a malignant cell. Or it could be a normal product that is always shed, but is somehow modified afterwards by tumor cells it comes in contact with. "There are a number of possibilities as far as the origin," said Davidson, "and this is one of the things we're studying in the lab right now. We're trying to find out more details of its structure by peptide mapping, and we're comparing it to other cellular products." His research team is also trying to develop a test with greater sensitivity through utilization of monoclonal antibodies. The work of Davidson and Bolmer suggests the important role that analytical technology can play in elucidation of the disease state, both in general and specific diagnosis and in monitoring the course of treatment. In addition, markers found by analytical methods could provide essential clues that may lead to a fundamental understanding of the chemical etiology of diseases such as cancer. Stuart A. Borman
