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Leflunomide is an anti-inflammatory and immunosuppressive agent which blocks proliferation of transformed cells and mitogen stimulated normal lymphocytes but does not block T cell signaling mechanisms at antiproliferative concentrations. These properties are consistent with a mechanism involving interference with nucleotide metabolism. Leflunomide had anti-proliferative activity against all cells tested here. The anti-proliferative activities could be reversed by addition of uridine or cytidine to the cultures although some species and cellular differences were observed. Purine nucleotides had no effect. Measurements of nucleotide pools in a human T cell line and mitogen stimulated rat spleen cells treated with leflunomide showed that leflunomide preferentially reduces pyrimidine nucleotide levels. These results indicate that inhibition of pyrimidine biosynthesis is responsible for the anti-proliferative effects of leflunomide.

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The efficacy of a new vaccine preparation against Epstein-Barr (EB) virus was investigated in cotton-top tamarins. The vaccine consists of fast protein liquid chromatography-purified EB virus membrane antigen glycoprotein of 340 Kd (MA gp340) mixed with a synthetic muramyl dipeptide adjuvant emulsified in squalane containing a pluronic polymer; it is suitable for both scaled-up batch production and eventual administration to man. Vaccinated tamarins rapidly developed ELISA detectable high titre antibodies to MA gp340, and their sera became strongly EB virus-neutralising. After challenge with a massive 100% carcinogenic dose of EB virus, the vaccinated tamarins had a strikingly low level of circulating EB virus-carrying mononuclear cells, in contrast to a control animal, and remained entirely free of tumours. This first-generation vaccine has thus been validated in experimental animals and the way opened for a phase I human trial.