IN-VIVO TREATMENT WITH A MONOCLONAL CHIMERIC ANTI-CD4 ANTIBODY RESULTS IN PROLONGED DEPLETION OF CIRCULATING CD4+ CELLS IN CHIMPANZEES

Chimeric M-T412 (cM-T412), an anti-CD4 antibody, was tolerated in chim panzees at a dosage of 5 mg/kg per day for up to 7 consecutive days, o r 5 mg/kg per dose, twice weekly for 4 weeks. All cM-T412-treated chim panzees showed a prolonged CD4 cell depression. Weak chimpanzee antibo dy responses to chimeric M-T412 were observed. One of the chimpanzees on the biweekly dosage regimen exhibited a hypersensitivity reaction i mmediately after receiving its seventh dose. Following supportive trea tment, the animal recovered and remained asymptomatic during the non-t reatment observation period. The hypersensitivity reaction was not an unexpected response considering the animal received repeated intermitt ent i.v. administration of a foreign protein. This animal also showed a chimpanzee antibody response to chimeric M-T412 after the seventh do se. Chimeric M-T412 also induced an anti-cM-T412 response in some of t he other animals. The level of this response was lower than the anti-m ouse responses observed in animals treated with murine anti-CD4. Moreo ver, the anti-cM-T412 response was mainly directed to idiotypic determ inants. The decrease in CD4+ cells observed for all chimeric M-T412-tr eated chimpanzees is an expected effect of the anti-CD4 antibody. The duration of this CD4+ cell decrease is, however, much longer than obse rved for other CD4-specific MoAbs described. No selective loss of eith er memory or naive CD4+ cells was observed after either the single, 7- day or twice-weekly treatments. The CD4+ cell depression was reversibl e, although individual variation in time to recovery was observed. The refore, cM-T412 could be a good candidate for clinical use in autoimmu ne conditions.