Reduction of Nitric Oxide with L–/Vc–Monomethyl Arginine in lnterleukin–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.