Tumor-specific antigens have been moving targets of cancer researchever since monoclonal antibodies were invented in 1975. Moving,because every time a cell biologist or oncologist announced finding aprotein unique to a given malignant tissue, it turned out that the sameantigen turned up elsewhere in the body, albeit in low concentrations.Nowadays, researchers prudently refer to "tumor-associated" ratherthan "specific" antigens, and of course many of these "associated"proteins are working near-wonders at piloting antibodies to theirdiagnostic or therapeutic targets.Late last month, the National Cancer Institute submitted a notice forpublication in the Federal Register. It seeks a commercialbiotechnology or pharmaceutical partner to develop its "TherapeuticApproaches for Breast Cancer . . . based upon a novel DNA bindingprotein to c-erbB-2.""Amplification and overexpression of the c-erbB-2. gene," reads theannouncement, "appears to play a role in the pathogenesis of humanbreast cancer and other cancers." Its product is a glycoprotein"believed to be a receptor."In March, NCI's Cancer Research and Development Center inFrederick, Md., filed a U.S. patent application titled, "erbB-2. PromoterBinding Protein in Neoplastic Disease" covering the invention. Its co-inventors are molecular biologist Razuiddin (his full name), a seniorscientist at Program Resources, Inc./DynCorp., also in Frederick, andmolecular biologist Fazlul Sarkar at Wayne State University pathologydepartment, Detroit.Companies awarded an exclusive or non-exclusive CooperativeResearch and Development Agreement (CRADA) to commercializethis discovery will obtain licenses to the pending patent.Sarkar, at Wayne State, Razuiddin explained to BioWorld Today,"initially screened biopsied breast tissues for the protein, anddetermined which samples were tumorous." The NCI scientist added,"I then applied my expertise to elucidating the DNA-binding protein."Raphe Kantor, who heads NCI's Office of Technology Development(OTD) at Frederick, told BioWorld Today that Program Resources,Inc., is a for-profit research-support facility "totally integrated intoNCI." He intimated that this company, a subsidiary of Dyn Corp., is apossible candidate for the CRADA that OTD is now offering.Another front-runner, said Razuiddin, is Oncor Inc., of Gaithersburg,Md., which has a DNA probe in development to detect amplification ofthe Her-2/neu gene in breast cancer cells. Kantor, Razuiddin and Sarkarpaid an all-day site visit to Oncor's up-coming breast-cancer screeningcenter last month.That company's long-established Her-2/neu gene, Razuiddin explained,is the name clinicians use for NCI's experimental erbB-2 "What's newabout erbB-2 is that never before has any person or any group found _not from the cell line, but directly from biopsied tissue taken from awoman's' breast _ a protein expressed only in the tumor biopsiedtissues, and not in normal tissues."Oncor's vice-president of research and development, biochemist JayGeorge, told BioWorld Today that his company submitted its Her-2/neu test for screening breast cancer to the FDA last February, seekingpre-marketing approval. "This test demonstrates," he explained, "bydetecting gene amplification, what a predicted course of clinicaloutcome would be for a patient positive to the Her-2/neu gene." Headded, "Razuiddin's gene encodes a regulatory protein that activatestranscription of the Her-2/neu gene."Topping the agenda of research and development collaboration with afuture designated CRADA partner, Razuiddin said, will be developingmonoclonal antibodies to the gene product, then cloning the gene thatencodes that protein. "To do so," he pointed out, "you need high-quality monoclonal antibodies," and added, "Unless we clone the gene,we really cannot define the in vivo situation. So cloning will be ourforemost target."He foresees applications in clinical practice as beginning with "a moresophisticated, biopsy-based, screening method for early-stage breastcancer." One aspect of initial joint research and development under aCRADA, Kantor suggested, will be to find the protein in biofluids,amenable to simple blood-testing.Second, "you can do histochemical studies, putting the biopsied tissueon a slide, and immediately you can see that the tumor is stained, thenormal, unstained."A third phase of launching marketable products would be treatment:developing agents to inhibit the protein, by gene therapy, antisense, orchemically synthesizing the peptide itself, then raising injectableantibody against it.Editor's Note: For information concerning NCI's offer of a CRADA toco-develop its breast-cancer protein, contact OTD licensing director,Raphe Kantor, at (301) 846-1501. n
-- David N. Leff Science Editor
(c) 1997 American Health Consultants. All rights reserved.