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TREATMENT OF DISSEMINATED NON SMALL CELL LUNG CANCER. Paul J Hesketh, Section of Medical Oncology, University Hospital, Boston MA, USA. Therapeutic options for the majority of patients with non small cell lung cancer (NSCLC) are unsatisfactory. Despite efforts to optimize local therapeutic modalities (surgery, radiotherapy), the cure rate for NSCLC remains a disappointing lo-12%, because most patients have disseminated disease at presentation. Thus significant improvement in outcome will only be realized with better systemic therapeutic approaches. A multitude of chemotherapeutic agents have been tested in NSCLC, but only a handful (cisplatin, mitomycin C, ifosfamide, vinblastine and vindesine), can be viewed as active, if activity is defined as an overall response rate of 2 15%. With single agents, however, the vast majority of responses are partial, of brief duration, and do not appear to confer any obvious survival advantage. Higher rates of response (30-60%) are fairly consistently seen when 2-3 of the active single agents are combined, most commonly with cisplatin based regimens. Complete responses remain uncommon however, and the survival benefits of combination chemotherapy remain unclear. Two recent studies attempting to define the survival advantage of combination chemotherapy have randomized patients between cisplatin based chemotherapy regimens and supportive care only. A modest prolongation of survival was seen in the chemotherapy arms in both studies, but only in one study was this difference statistically significant. Clearly, better therapeutic approaches are needed. A number of potential options will be discussed. One approach has been an attempt to optimize the use of conventional chemotherapeutic agents by exploring dose intensification, alternative administration schedules or pharmacologic modulation. The search for new active agents has yielded a number of drugs with promising activity, including edatrexate, VM-26, vinorelbine and carboplatin. The use of biologicals either alone or combined with chemotherapy offers another potentially useful approach.

IMNCJNOTOXINS FOR SHALL CELL LUNG CANCER: RESULTS OF IN VITRO INVESTIGATIONS. Stahel R.A., Wawrsynczak E., Collinson A., Zangemeister U., Lehmann H-P., Waibel R. Division Of Oncology, Department of Medicine, University Hospital, Zurich, Switzerland: Drug Targeting Laboratory, Institute of Cancer Research, Sutton, Surrey, UK: and Immunogen, Cambridge, MA, USA.

Wonoclonal antibodies have allowed to identify cell surface antigens on small cell lung cancer which to SOIW degree are differentially expressed between small cell carcinoma cells and normal tissues. The potential of some of these antibodies to form cytotoxic agents with the ricin A chain was examined with an indirect in vitro screening procedure. Monoclonal antibodies recoonizins the small cell carcinoma cluster-w4 and &us&-5A antigens mediated the toxic effects of ricin A chain well, while other antibodies lacked such an effect. Antibody SWAll against cluster-w4 was chemically conjugated to ricin A chain and examined for in vitro cytotoxicity, where selective CytotOXicity with an IC5O of 6x10-l I M could be incorporation

demonstrated by a leucin assay. Antibody SEN31 was

conjugated to chemically modified ~("blocked~~) whole ricin. In vitro SEN-31 blocked ricin h a selective cytotoxicity with an IC5u at lo -?P M (thymidine incorporation assay). Clonins assays -with ~~~ same conjlugate IC60 at 4x10 . At concentrations of th;" survivin _s fraction of antigen positive cells was 10 while that of antigen negative

cells was 6x10 12 . These in vitro investigations demonstrate the potential of immunotoxins for the development of new forms of therapy in small cell lung cancer.

SMALL CELL LUNG CANCER (SCLC) ANTIGENS ARE EXPRESSED DIFFERENTLY ON HUMAN CONTINUOUS CULTURED CELL LINES REPRESENTING SCLC “CLASSIC,” “VARIANT,” AND CARCINOID PHENOTYPES.

KOROS. A.M.C., ATCHISON, R.W.. and MITCHELL, D.L. UNIVERSITY OF PITISBURGH, GRADUATE SCHOOL OF PUBLIC HEALTH, PITTSBURGH. PENNSYLVANIA. U.S.A. 15261

The panel of 98 monoclonal antibodies (MOABS), (mouse or rat) provided by the Second International Workshop on Small Cell Lung Cancer Antigens was tested by indirect immunofluorescence and flow cytometry using prototype cell lines [NCI-H69 (SCLC “classic”), NC&N417 (“variant”), NCI- H727 (carcinoid) (A. F. Gazdar ti d Bethesda, MD] as well as normal human peripheral blood lymphocytes (PBL) and sea urchin coelomocytes [Koros, A. M. C. Int. J. Neurosci. 48:161 (1989).] All cells had some reactivity with some of the MOABS. There is however, differential expression of antigens amongst the prototype cell lines which may provide a useful method for phenotyping human lung cancers. In contrast to our earlier observations of neuroendocrine markers (CD56, CD57) on SCLC, neuroendocrine cells, human natural killer cells, and sea urchin coelomocytes, few (14/50) antigens identified by the present panel appear to be evolutionarily conserved. Those MOABS which do not react with normal PBL should be tested further for possible utility as therapeutic agents in patients whose tumors have escaped conventional therapy.

DETAILEO EPITOPE MAPPING OF LUNG CANCER ASSOCIATED CARBOHYDRATE ANTIGENS DETECTED BY AWTIBOOIES OBTAINED FROM VARIOUS LABORATORIES. c.M. Andrews, N.S. Seiler, and J.L. Waanani BioCarb Inc, Gaitharsburg, MD, USA Carbohydrate sequences occur in both glycolipids and glycoproteins on all cell surfaces and on excreted glycoconjugatas such as mucins. These oligosaccharide sequences change during development, and in adults constitute antigens responsible for many of the heritable blood groups. ouring tumorogenesis of a particular tissue, glycosylation may revert to an earlier developmental form found in fetal precursor cells. As these structures are immunogenic, many cancer-associated antigens submitted to d lung cancer workshop from various laboratories were screened by an enzyme-linked immunoassay for binding to synthetic glycoproteins produced by coupling chemically-defined oligosaccharide haptens to either bovine or human serum albumin. The 34 different synthetic glycoprotains that were screened contain the following carbohydrate structures: "T-antigen", lactose, mclibiose, maltose, cellobiose, 2'-fucosyllactosamine, globotriose, A-trisaccharide, B-trisaccharida, chitotriose, 38-sialyllactose, 6'-sialyllactose, Manol-3Man~l-4(GlcNAc), Ley-tetrasaccharide, gangliotetraose, lacto-N-tetraose, la&o-N- neotetraose, A-tetrasaccharide, globotetraose, Manal-2Man41-3Man,81-4(GlcNAc), la&o-N- fucopentaosa I, lacto-N-fucopentaose II, lacto-N fucopentaose III, sialyllacto-N-tetraose a, sialyllactotetraose b, sialyllacto-N-neotetraose c, lacto-N-difucohexaose I, la&o-N-he%aose, lacto-N-neohexaose, sialyllacto-N-fucopentaose