title: Reduction of nitric oxide with L-/NG-monomethyl arginine in interleukin-2 and anti-CD3 monoclonal antibody combination therapy.
abstract: We evaluated nitric oxide induction in antitumor therapy consisting of anti-CD3 monoclonal antibody (anti-CD3) and interleukin-2 (IL-2), then determined the effect of nitric oxide reduction with L-N(G)-monomethyl arginine (LNMA) on the therapeutic methods. Female C57BL/6 mice, MCA102 (a non immunogenic, NK-resistant murine fibrosarcoma cell line), and 145-2C11 (hamster anti-murine-CD3 mAb) were utilized in an experimental hepatic metastasis model developed by injecting a tumor cell suspension into the spleen of mice. A marked increase in serum NO2 (-) + NO1 was observed at 19 hours after anti-CD3 (10 μ, IV) and additional IL-2 administrations (40 × 10(1) U, twice, If) induced a further increase. The NO2, + NO3- elevation in spot urine in the combination therapy was not suppressed with LNMA at a dose of 100 μg/h but was significantly lowered at 300 μg/h. The efficacy of the anti-CD3 + IL-2 therapy was not diminished by LNMA administration either at 100 μg/h or at 300 μg/h.
authors.affiliation: Department of Urology, National Defense Medical College, Tokorozawa, Japan.
authors.forename: F
authors.initials: F
authors.lastname: Nakajima
authors.forename: T
authors.initials: T
authors.lastname: Asano
authors.forename: M
authors.initials: M
authors.lastname: Hayakawa
authors.forename: H
authors.initials: H
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D007167:Immunotherapy / Q000379:methods*; D007376:Interleukin-2 / Q000494:pharmacology*; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009569:Nitric Oxide / Q000378:metabolism*; D019323:omega-N-Methylarginine / Q000494:pharmacology*
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D017252:CD3 Complex; D004791:Enzyme Inhibitors; D007376:Interleukin-2; D019323:omega-N-Methylarginine; D009569:Nitric Oxide
keywords: antitumor therapy; cytokine therapy; nitric oxide