Document GKxj5D7kY57nn9nanLdKxoBNx

URL 04917 More progress in cancer TAA has yet been found that is present on all cells in a given tumor. "The fun damental diversity and entrepreneurial diagnosis and treatment character of tumors," says Green, "means that there is enormous biochem ical variability in their expression." With an eye toward development of While there have been dramatic reduc the distorted proliferation of derived monoclonals for diagnosis, researchers tions in the incidence of certain cancers, leukocytes, or white blood cells. But are focusing on the biodistribution of the overall numbers have changed little there are many types of white blood intravenously administered antibodies during the past 40 years: Cancer re cells and, therefore, many types of leu to develop techniques that reduce their mains the second leading cause of death kemia, each of which can behave differ nonspecific distribution in the body. Ef in the U. S. However, "Cancer Pro ently and respond differently to treat forts also are focused on increased de gress," a conference sponsored by Com* ment However, since leukemic cells livery of monoclonals to microscopic tu munitech (Yorktown Heights, N. Y.) and often retain the surface antigens associ mor deposits in lymph nodes. held in New York City earlier this ated with the normal cells from which Also showing great promise as diag month, zeroed in on developments in they were derived, monoclonals specific nostic tools are DNA probes, reports cancer diagnosis and therapy, and deliv for those antigens can be used to identi Oncor's Turner. Such probes--small ery systems for cancer drugs. And in fy the type of leukemia. Such monoclon pieces of DNA that recognize specific those areas, reported Robert C. Hickey, als, says Mhatre, may allow head of surgery at M. D. Anderson Hos early diagnosis and better sur pital and Tumor Institute (Houston, vival rates. Tex.), "progress is being made." Other types of monoclonals This year, it is estimated, 876,000 new that Mhatre says may be de cases of cancer will occur in the U. S. veloped in the next few years: and 453,000 people will die of the dis antibodies specific for major ease. In addition, approximately 5 mil cancers of such organs as lion patients now require monitoring-- lungs, breasts and colons to either for therapy or because they have help determine the origin of metastases; On the horizon: Monoclonal antibodies that can Identify specific tumor antigens antibodies to determine whether a cell is malignant. Agreeing with Mhatre, Allan M. Green, director of nuclear medicine at Boston University had a malignancy that is in remission. Medical Center, says that iden Yet annual sales of in vitro cancer di tification of tumor-associated agnostics, says Stephen Turner, presi antigens (TAA)--antigens spe dent of Oncor (Gaithersburg, Md.), are cifically associated with tumor less than $100 million. "Clearly," says cells and not with normal Turner, "there's a need for new and cells-^is the key to the success unequivocal diagnostic tools." of monoclonals in diagnosis. Diagnosis. An ideal approach to the The difficulty in such identi definitive diagnosis of cancer, in the fication, however, is illustrated view of Nagesh S. Mhatre, president of by carcinoembryonic antigen Becton Dickinson Immunocytometry (CEA), says Green. CEA is per Systems (Mountain View, Calif.), would haps the best known and char seem to require labeled monoclonal anti acterized TAA. And while CEA bodies--antibodies that bind to a single is clearly associated with colon antigen--that selectively and specifical tumors, it is also found on oth ly react to tumor cells without reacting er tumors of the gastrointesti O'Connor New perspectives on treating solid tumors to such cells' nontumor counterparts-- nal (GI) tract and on such non- i.e., normal cells. But most tumors ex GI tumors as cancer of the breast. genes or segments of DNA--can detect press the same cell surface antigens as Further, it is associated with nonmalig- relocations of DNA sequences that re expressed by normal cells. Few mono nant diseases such as acute hepatitis. late to tumor development. An example clonal antibodies, therefore, are truly This nonspecificity, says Green, ham is the rearrangement of a specific cell- tumor-specific, although some are tu pers the use of CEA in the diagnosis of surface receptor gene that occurs in mor-associated and reasonably selective. colon cancer. two distinct types of immune system Thus, current applications generally Moreover, diagnosis of the exact loca white blood cells--B and T lympho use antibodies to antigens expressed on tion of colon tumors is impeded by the cytes--as they turn from normal to can the tumor cell and the normal cell. fact that CEA isn't firmly anchored to cer cells. Probes developed by Oncor Monoclonal antibodies targeted for leu the tumor cell surface. Instead, it is that detect this rearrangement, says kemic cells offer a good example of shed into the bloodstream where it can Turner, can be used in the early identifi how the system would function. Leuke interact with monoclonals far from the cation of tumorous T and B cells in lym mia is a malignant disease of the blood- tumor site. phoblastic leukemia. The probes. Turner forming organs and is characterized by Other TAAs also are shed. And no says, can detect as little as 1-3% tumor 9B Chemical Week/June 26. 1985 UR10491U cells in a mixed specimen. Other Oncor probes also can detect oncogenic viruses. Those strains of human papil loma virus now closely associ ated with the onset of cervical cancer can be detected, as can human T lymphotropic virus III (HTLV-III), the virus closely linked to acquired immune de ficiency syndrome (AIDS). DNA probes, says Turner, "provide the only current means to gauge active papilloma or HTLV-III infection." Reorganize. What's more, says Turner, probe technology will "deliver a new kind of can cer patient data that will be come mandatory for diagnostic accura cy." He adds that ``over time it will reorganize the basis by which tumors are identified and classified." Monoclonal antibodies also are gain ing recognition in cancer therapy. Near term, their greatest potential, says Beeton Dickinson's Mhatre, is in transplan tation to treat bone marrow cancer. The rationale for such transplantation is that although it may be possible to kill all the tumor cells in bone marrow with a dose of radiation or chemotherapy, an adequate dose also would destroy the patient's immune system, which is gen erated by bone marrow. Yet, if normal bone marrow could be injected into a cancer patient following high-dose therapy, such treatment could be successful. The problem is that bone marrow from another person---even if closely matched for hisn'compatibiUty-- has immune system ceus that will rec ognize the new host as foreign and will attack host tissues, a condition known as graft versus host (GVH) disease. One approach that has worked well in mice and has been used with increasing success in people is to remove T cells-- the cells that initiate GVH disease-- from donor marrow before injection. Removal can be accomplished using monoclonals specific for T cells. Meth ods now being tested use such monoclonals conjugated to toxins and mono clonals attached to magnetic beads or columns. The best technique, says Mhatre, should be determined within the next two years. The use of monoclonals for direct in vivo treatment of cancer--the "magic bullet" concept--has proved elusive, says Mhatre. The reason is the same difficulty that has hindered monoclonal antibodies in diagnosis: Truly tumorspecific monoclonals have been difficult to produce. But if such monoclonals can be devel oped, several approaches could render them toxic to cancer cells. Monoclonals can be coupled to immunotoxins, such as ricin, to radioactive isotopes or to cancer drugs like daunomycin. In fact, ricin and daunomycin are now being used extensively in clinical trials. In ad dition, the naked monoclonal can mark Probe technology will deliver a new kind of data `mandatory for diagnostic accuracy' tumor cells for destruction by the host immune system. However, work with monoclonals for in vivo therapy "is mostly in its infan cy," says Mhatre. He adds that the most promising approaches will not be determined for several years. Another potential cancer therapeutic agent, the human protein tumor necro sis factor (TNF), is being explored by a host of firms active in genetic engineer mg. Timothy E. O'Connor, associate in stitute director for scientific affairs at Roswell Park Memorial Institute (Buf falo, N. Y.), says that TNF presents a different set of problems. Although nontoxic to a wide range of human cells, the compound can destroy a num ber of the most lethal human and ro dent tumors, including melanoma, lung carcinoma, colon carcinoma and breast carcinoma. At the same time, TNF is not effective against other cancers, includ ing other breast carcinomas, bladder carcinoma and erythroleukemias. But it is toxic to the intraerythrocyte parasite of malaria and to microorganisms of the genera Klebsiella and Listeria. Examination of TNF's "molecular mechanisms of action on tumor cells" will receive close attention in the com ing year, says O'Connor. The com pound, he adds, could "open new perspectives" on treat ment of solid tumors. Receiving equal billing with new diagnostic and therapeutic tools are new systems for de livering cancer drugs. Deme- trious Papahadjoupoulos, chair man of the scientific advisory board for Liposome Technol ogy (Menlo Park, Calif.), re ported that liposome encapsu lation of two highly toxic cancer drugs, Adriamycin dox orubicin hydrochloride and am photericin B, drastically re duced adverse toxic effects. In both cases, says Papahadjou poulos, animal experiments have shown promising results and clini cal trials have begun. When injected intramuscularly into the body, liposomes release a drug slowly and thus act as a molecular infu sion pump. The vesicles consist of a thin lipid membrane that surrounds a central aqueous space that contains water-solu ble drugs. The lipid membrane can car ry lipid-soluble drugs. Moreover, lipo somes can be made to interact with certain cells by attaching specific anti bodies to their surface. Other delivery systems were high lighted by Jeffrey H. Berg, vice-presi dent of PA Technology (Hightstown, N. J.). Increasingly, says Berg, chemo therapy is being administered by such systems as external and implanted infu sion pumps and vascular access ports. Infusion pumps. Currently, about 30 companies produce external infusion pumps. Such pumps are based on two different infusion regimens. The closedloop system regulates dosage by auto matic sensing of physiological parame ters. Open-loop devices operate on a preset flow rate or are programmable with a variable flow rate usually associ ated with a diurnal cycle. The pumps are used chiefly for delivering insulin but can be adapted to administer che motherapeutic agents. However, only a few firms--including Deltec Systems, Autosyringe, Pancretec and Conned-- have focused on such adaptations. Implanted infusion pumps, on the oth er hand, are being developed largely for cancer treatment These pumps are gen erally placed in the abdominal wall or the subclavicular area. The rationale is that smaller total doses of toxic drugs are needed to achieve the same effect as with systemic infusion. Infusaid (Sharon, Mass.) is the only company with Food and Drug Adminis tration approval for the sale of such 100 Chemical Week/June 36. 1965 pumps and has sold about 14,000. Med CUSTOM SERVICES me 5-7 ant 'ith cai ARE YOU IN NEED OF TOLLING liti- es- 5ir- OR CUSTOM MANUFACTURING n30. FA CILITIES IN ENGLAND? tronic (Minneapolis) and Shiley (Irvine, Calif.) are clinically testing implanted pumps, as is Cordis in Europe. ,n addi tion, a number of leading pacemaker producers are developing these devices. Use of the Infusaid pump in the treatment of liver cancer has been in tensively studied. The pump continuous ly administers 5-fluorodeoxyuridine di rectly into the hepatic artery in patients with unresectable solid liver tumors. The method results in greater reduction ee Lankro Chemicals Limited--an affiliate of Diamond Shamrock Chemicals Company, in tumor mass, says Berg, and im Tn to Dallas. Texas--has production facilities immediately available for: proved median survival rates relative to :al --Alkoxylation conventional intravenous therapy. er --Sulfation/sulfonation h- --Isocyanate prepolymers Vascular access ports also have be come a popular infusion method for che --General purpose glass and stainless steel reactor systems up to 3000 gallons motherapy, says Berg. The ports, im The facilities, available because of industry rationalization, are located at the company's plant in Manchester, England. planted under the skin, consist of a self-sealing injection port and a catheter URL 04919 The production site is close to major expressways, has ample bulk liquid storage capacity, is staffed with qualified professional engineers and chemists, and offers well equipped services to meet your needs. Lankro Chemicals, a company with sates of $75 million, has over 500 employees, and operates trom Manchester, with a smaller site near Brussels, Belgium. The company is active in tour main business areas: polymer additives, polyurethane chemicals, surfac tants and radiation curing chemicals. Drug delivery systems include sell-sealing vascular access ports and implanted pumps' for drug delivery to selected sites. Infu For further details contact: said, Pharmacia (Piscataway, N, J.) and Cormed are marketing products. Med Lankro J.P. Blrkinahaw Director of Operation* Lankro Chemical* Ltd. P.O.BoxI Eccias, Manchester M30 0BH tronic and Davol (Cranston, R. I.) are expected to enter the market. More and more, says Berg, vascular access ports will be used in conjunction with external infusion pumps for drug delivery. In fact, manufacturers are Tel: (44) SI 789 7300 Talas: 587725 LANKRO G now developing tubing and needle sets to interface the systems--a develop ment that poses a "serious competitive threat" to the future of implantable in fusion pumps, Berg says. The relative costs, he adds, are approximately $2,500 CHEMICALS WANTED- CHEMICALS WANTED- for the external pump/port system ver sus $8,000 for an implanted pump. Wanted -- Your Surplus chemicals, phar maceuticals dyes. etc. Chemisales, Inc. 10727 180th St. Jamaica, NY 11433 (718) 6580400. We Buy Surplus Chemicals, Pigments, dyes, resins, plasticizers, solvents, etc. Eastern Color & Chemical Co., Inc., 65 Roosevelt Ave. Dept. A. P.0. Box 1029. Valley Stream U., N.Y. 11582. 516/791-4445. Controlled release. Moreover, vascu lar access ports may find use in controiled-release drug delivery, 3ays Berg.\ For example, Pharmacia envisions using its system to deliver Spherex micro Your Surplus is our inventory. Wa buy all resins, pigments, solvents, dyes and plas ticizers, Pyramid Chemical Sales Co.. 1035 Virgmia Drive. Fort Washington. Pa. 19034. 215-542-9292. Cash for Surplus Plastics, Chemicals, dyes, plasticizers, oils, etc. Morgan Chemicals. 5500 Main St.. Wifliamsville, NY 14221. (716)632-4000. spheres for treating liver cancer. The spheres are tiny starch beads that con tain either bw-chloroethylnitrosourea or mitomycin C, which are released when the starch is broken down by amylase in the blood. The system is in clinical We will buy surplus chemicals, resins, oils, colors, solvents, plasticizers, specialties, in termediates. etc. The Rambach Company. 57 McWhorter St.. P.Q. Box 5300. Newark, NJ 07105. (201) 589-7774 Resyn Corp. will buy your surplus chemicals and resins. Resyn Corp., P.0. Box 63. 1540 W. Blancke St., Linden. NJ 07036. 201-862-8787. studies at the University of Michigan (Ann Arbor) and four other institutions. The take-home message from the con ference: Although progress appears to be painfully slow, continuous advances are being made. And some participants Solvents -- Sell us your by-product sol vents for recycle. Legal disposal of nonre- cyclables. Eighteen years dependable ser vice. Marisol. Inc.. 125 Factory Lane. Midd lesex. NJ 08846. Tel. 201/469-5100. Wanted Surplus Chemicals, etc. Bonmar Chemical Co., P.O. Box 494, Fair Lawn, NJ. 07410, 201-791-2448, Telex: 13-0434. expressed considerable optimism. Green of Boston University Medical Center sums up: "The future, as Herbert Hoo ver observed, lies before us." S.J SPALDING