Modified anti-CD3 therapy in psoriatic arthritis: a phase I/II clinical trial.
Modified anti-CD3 therapy in psoriatic arthritis: a phase I/II clinical trial.
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发表时间：
2002-09
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通讯作者：
T. Utset;J. Auger;D. Peace;R. Zivin;Danlin Xu;L. Jolliffe;M. Alegre;J. Bluestone;M. Clark
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作者：
T. Utset;J. Auger;D. Peace;R. Zivin;Danlin Xu;L. Jolliffe;M. Alegre;J. Bluestone;M. Clark
目的用耐受致病性淋巴细胞的疗法治疗自身免疫性疾病可能会避免长期的全面免疫抑制。在体外，抗鼠CD 3单克隆抗体的非Fc受体结合衍生物耐受1型T细胞并刺激2型T细胞。最近，已经描述了抗人CD 3 Mab OKT 3的人源化非FcR结合衍生物huOKT 3 γ 1（ala-ala）。我们推测这种单克隆抗体可能是安全和有效的治疗1型T淋巴细胞介导的慢性自身免疫性疾病，如银屑病关节炎（PsA）。方法在I/II期试验中，7例PsA患者接受每日递增剂量的huOKT 3 γ 1（ala-ala）治疗12至14天。使用压痛和肿胀关节的数量以及视觉模拟疼痛量表来评定入组时以及治疗后第30天和第90天的疾病活动性。结果在第30天，7名患者中有6名患者的关节炎数量改善≥ 75%，患者疼痛评分平均改善63%。6例应答者中有2例在第90天持续改善。用初始剂量<或= 1 mg治疗的患者没有显著的副作用，也没有可检测到的血清细胞因子增加。1例接受4 mg治疗但未递增的患者出现与白细胞介素10升高相关的轻度细胞因子释放症状。最大剂量4 mg治疗后发生一过性T细胞耗竭，第30天消退。2例患者出现抗独特型抗体;然而，疗效未同时降低。结论huOKT 3 γ 1（ala-ala）可能是治疗银屑病的有效药物。
OBJECTIVE Treatment of autoimmune diseases 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 autoimmune diseases such as psoriatic arthritis (PsA). METHODS In a Phase I/II trial, 7 patients with PsA 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 pain scale were used to rate disease activity at entry and Day 30 and Day 90 after treatment. RESULTS At Day 30, 6 of 7 patients had > or = 75% improvement in the number of inflamed joints and an average 63% improvement on the patient pain scale. Two of 6 responders had sustained improvement at Day 90. No patient treated with an initial dose < or = 1 mg had significant side effects, nor did they have detectable increases in serum cytokines. One patient treated with 4 mg without escalation developed mild cytokine release symptoms associated with elevation of interleukin 10. Transient T cell depletion occurred following treatment with the maximum dose of 4 mg, which resolved by Day 30. Antiidiotypic antibodies developed in 2 patients; however, there was no concurrent decrease in efficacy. CONCLUSION These data indicate that huOKT3gamma1(ala-ala) may be useful in treating PsA.