Modified anti-CD3 therapy in XXXX : a phase I/II clinical trial.

@entity1 @entity5144 @entity158 @entity688 @entity792
OBJECTIVE: Treatment of @entity792 with therapies that tolerize pathogenic lymphocytes may obviate the need for longterm global immunosuppression. In vitro, non-Fc receptor binding derivatives of anti-murine CD3 monoclonal antibodies tolerize type 1 T cells and stimulate type 2 T cells. Recently, a humanized non-FcR binding derivative of the anti-human CD3 Mab OKT3, huOKT3gamma1(ala-ala), has been described. We hypothesized that this Mab may be safe and efficacious in the treatment of type 1 T lymphocyte mediated chronic @entity792 such as @entity5144 ( @entity5144 ). METHODS: In a Phase I/II trial, 7 @entity1 with @entity5144 were treated with escalating daily doses of huOKT3gamma1(ala-ala) for 12 to 14 days. Number of tender and swollen joints and a visual analog @entity158 scale were used to rate disease activity at entry and Day 30 and Day 90 after treatment. RESULTS: At Day 30, 6 of 7 @entity1 had > or = 75% improvement in the number of inflamed joints and an average 63% improvement on the @entity1 @entity158 scale. Two of 6 responders had sustained improvement at Day 90. No @entity1 treated with an initial dose < or = 1 mg had significant side effects, nor did they have detectable increases in serum cytokines. One @entity1 treated with 4 mg without escalation developed mild cytokine release symptoms associated with elevation of @entity688 . Transient T cell depletion occurred following treatment with the maximum dose of 4 mg, which resolved by Day 30. Antiidiotypic antibodies developed in 2 @entity1 ; however, there was no concurrent decrease in efficacy. CONCLUSION: These data indicate that huOKT3gamma1(ala-ala) may be useful in treating @entity5144 .
