Effects of monoclonal anti-lymphocyte antibodies in vivo in monkeys and humans.

The safety and efficacy in vivo of three rat monoclonal anti-lymphocyte antibodies has been tested in cynomolgus monkeys. One IgM antibody, CAMPATH 1, was found to cause rapid but transient lymphopenia associated with consumption of complement. Two other antibodies with the same specificity, YTH 34.5 (IgG2a) and YTH 86.1 (IgG2c), had little effect. No acute or chronic toxic effects were associated with administration of any of the antibodies. CAMPATH 1 was used in a Phase I clinical trial for immunotherapy of two patients with terminal malignant lymphoid disease. It had no detectable toxic effects although it caused disappearance of circulating lymphocytes and consumption of complement. An inadequate rate of synthesis of complement components was a limitation to therapy in these patients with very large tumour burden, but might not be a major problem if antibody therapy were used at an earlier stage of the disease. CAMPATH 1 may also be useful as an immunosuppressive agent.