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Prophylaxis and treatment of experimental tumors with the immunomodulator LS 2616
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ACTIVITY OF THE IMMUNOMODULATOR FCE 2 0 6 9 6 IN EXPERIMENTAL MODELS OF AUTOIMMUNITY. A.M. Isetta, M.C. Fornasiero, M. Ferrari and D. Trizio. Farmitalia Carlo Erba Research Center, Nerviano, Miiano, Italy. FCE 20696 is a synthetic compound that has been shown to induce suppressor cells after repeated oral administrations in mice. We have tested it by oral route in three established models of autoimmunity. EAE has been induced in Lewis rats and FCE 20696 given for two weeks before and three weeks after the administration of the encephalocytogen. Adjuvant arthritis was induced in rats and FCE 20696 given for four weeks from the day of the induction of the disease. Female NZB/WF 1
mice were treated with FCE 20696 biweekly trou-
ghout their life, starting from nine weeks of age. The results show that in EAE at doses ranging from 1 to 5 mg/Kg FCE 20696 reduces the symptoms of the disease and protects some animals (20-50%) from becoming ill. In the adjuvant arthritis model animals treated with ] mg/Kg had reduced inflammatory lesions in both the injected and controlateral legs. NZB/WF 1 mice treated with 1.5 mg/Kg lived 12 weeks longer than controls and proteinuria of 500 mg/ml or more was delayed for 8 weeks in treated mice. This drug has a definite value in experimentai autoimmunity and seems a good candidate for clinical testing. IMMD~E MODULATION BY CIAMEXONE U. Bicker, J. Mertin, W. Pahlke Boehringer Mannheim GmbH Product Development, Mannheim, FRG Ciamexone, a further derivative of the immunomodulating compound Azimexone, was tested in various experimental assays. It was found that Ciamexone increases the delayed type hypersensitivity reaction in Oxazolone sensitized mice, increases the survival rate of immunocomprimized, Cyclophosphamide treated or X-irradiated mice which have been effected with Candida albicans. Cellularity of the bone marrow and the peritoneal cavity was found to be increased after Ciamexone treatment of normal or Cyclophosphamide treated mice. On the other hand the local graft versus host reaction was significantly suppressed by Ciamexone treatment even at the 0.5 mg/kg dose level. In this assay, Ciamexone was more effective than the immunosuppressive drug Cyclosporin A. Ciamexone is very well tolerated both in experimental animals and in men. Therefore we feel that Ciamexone might be a good candidate for the treatment of patients with various autoaggressive syndroms.
PROPHYLAXIS AND TREATMENT OF EXPERIMENTAL TUMORSWITH THE IMMUNOMODULATORLS 2616 .
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Terje Kalland, Alena Makslmova and Torbjorn Stalhandske , Department of Anatomy, Unlverslty of Lund and AB LEO Research Laboratorles , Helslngborg, Sweden. •
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Thequinoline-3-carboxamideLS 2616 has been shown to be an e f f e c t i v e stimulator of NK a c t i v i t y . Moreover, the substance enhance the p r o l i f e r a t i v e response to T c e l l mitogens and augments delayed h y p e r s e n s i t i v i t y responses. In the present study LS 2616 was shown to e f f i c i e n t l y protect against a r t i f i c i a l metastases a f t e r iv i n j e c t i o n of BI6-FIO c e l l s to syngenic mice. LS 2616 also s i g n i f i c a n t l y reduced the number of lung metastases when administered a f t e r the establishment of e i t h e r a r t i f i c i a l l y produced or spontaneous metastases. Continous administration of LS 2616 from the time of sc tumor inoculation also reduced the frequency of growing tumors. Selective e l i m i n a t i o n of various lymphoid e f f e c t o r c e l l s and experiments with mutant mice indicate that various e f f e c t o r functions operate in the various experimental s i t u a t i o n s .
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ACTIVITY OF THE IMMUNOMODULATOR FCE 2 0 6 9 6 IN EXPERIMENTAL MODELS OF AUTOIMMUNITY. A.M. Isetta, M.C. Fornasiero, M. Ferrari and D. Trizio. Farmitalia Carlo Erba Research Center, Nerviano, Miiano, Italy. FCE 20696 is a synthetic compound that has been shown to induce suppressor cells after repeated oral administrations in mice. We have tested it by oral route in three established models of autoimmunity. EAE has been induced in Lewis rats and FCE 20696 given for two weeks before and three weeks after the administration of the encephalocytogen. Adjuvant arthritis was induced in rats and FCE 20696 given for four weeks from the day of the induction of the disease. Female NZB/WF 1
mice were treated with FCE 20696 biweekly trou-
ghout their life, starting from nine weeks of age. The results show that in EAE at doses ranging from 1 to 5 mg/Kg FCE 20696 reduces the symptoms of the disease and protects some animals (20-50%) from becoming ill. In the adjuvant arthritis model animals treated with ] mg/Kg had reduced inflammatory lesions in both the injected and controlateral legs. NZB/WF 1 mice treated with 1.5 mg/Kg lived 12 weeks longer than controls and proteinuria of 500 mg/ml or more was delayed for 8 weeks in treated mice. This drug has a definite value in experimentai autoimmunity and seems a good candidate for clinical testing. IMMD~E MODULATION BY CIAMEXONE U. Bicker, J. Mertin, W. Pahlke Boehringer Mannheim GmbH Product Development, Mannheim, FRG Ciamexone, a further derivative of the immunomodulating compound Azimexone, was tested in various experimental assays. It was found that Ciamexone increases the delayed type hypersensitivity reaction in Oxazolone sensitized mice, increases the survival rate of immunocomprimized, Cyclophosphamide treated or X-irradiated mice which have been effected with Candida albicans. Cellularity of the bone marrow and the peritoneal cavity was found to be increased after Ciamexone treatment of normal or Cyclophosphamide treated mice. On the other hand the local graft versus host reaction was significantly suppressed by Ciamexone treatment even at the 0.5 mg/kg dose level. In this assay, Ciamexone was more effective than the immunosuppressive drug Cyclosporin A. Ciamexone is very well tolerated both in experimental animals and in men. Therefore we feel that Ciamexone might be a good candidate for the treatment of patients with various autoaggressive syndroms.
PROPHYLAXIS AND TREATMENT OF EXPERIMENTAL TUMORSWITH THE IMMUNOMODULATORLS 2616 .
.
.
.
o
*
Terje Kalland, Alena Makslmova and Torbjorn Stalhandske , Department of Anatomy, Unlverslty of Lund and AB LEO Research Laboratorles , Helslngborg, Sweden. •
.
.
*
.
Thequinoline-3-carboxamideLS 2616 has been shown to be an e f f e c t i v e stimulator of NK a c t i v i t y . Moreover, the substance enhance the p r o l i f e r a t i v e response to T c e l l mitogens and augments delayed h y p e r s e n s i t i v i t y responses. In the present study LS 2616 was shown to e f f i c i e n t l y protect against a r t i f i c i a l metastases a f t e r iv i n j e c t i o n of BI6-FIO c e l l s to syngenic mice. LS 2616 also s i g n i f i c a n t l y reduced the number of lung metastases when administered a f t e r the establishment of e i t h e r a r t i f i c i a l l y produced or spontaneous metastases. Continous administration of LS 2616 from the time of sc tumor inoculation also reduced the frequency of growing tumors. Selective e l i m i n a t i o n of various lymphoid e f f e c t o r c e l l s and experiments with mutant mice indicate that various e f f e c t o r functions operate in the various experimental s i t u a t i o n s .
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