PHASE IA/B TRIAL OF ANTICD3 AND INTERLEUKIN 2

LAK细胞和IL-2的初步临床试验与 约20%的肾脏疾病患者出现部分或完全反应 细胞癌和黑色素瘤。然而，抗肿瘤药物的比较 IL-2单独与IL-2联合LAK细胞的活性显示 最好只是从LAK细胞中获得很小的临床益处。A最近 在Frederick CRB使用IL-2和体外完成了I期试验 抗CD3激活的T细胞显示出出乎意料的低应答率。 这项试验的一个限制是，只有 在外周血液中循环可以被激活。临床前研究 提示在CD8+细胞是排斥反应模式的肿瘤中， 抗CD3和IL-2的注射时机至关重要。基于 考虑到这些因素，我们建议对免疫活性进行管理 肿瘤患者体内抗CD3的剂量。同时给予丸剂和 持续输注IL-2。这项研究的目标是：确定 抗CD3抗体能否安全地与IL-2联合应用； 确定该方案的毒性，以测量选择性 免疫调节作用；观察任何抗肿瘤反应，并确定 活化的T淋巴细胞能否在体内实现扩增 这种方法。PTS。将获得抗CD3(400、800、1200、800亩/平方米)， IL-2静脉滴注0.75mU/m2，IL-2推注1.5mU/m2。 第四军团将接受环磷酰胺。12分。已经加入了这项研究以 约会。已经有两次公关了。有明显的毒性 包括低血压、寒战、发烧和代谢性酸中毒。这个 低血压比服用类似剂量的IL-2更明显 独自一人。这些都是可控的。我们计划累积总共24分。

Initial clinical trials with LAK cells and IL-2 are associated with partial or complete responses in approximately 20% of patients with renal cell carcinoma and melanoma. However, the comparison of the antitumor activity of IL-2 alone versus IL-2 in combination with LAK cells showed at best only a small clinical benefit from the LAK cells. A recently completed phase I trial at the Frederick CRB using IL-2 and in vitro anti-CD3 activated T cells revealed an unexpectedly low response rate. One limitation of this trial is the fact that only cells that are circulated in the peripheral blood can be activated. Preclinical studies suggest that in a tumor in which CD8+ cells are the mode of rejection, the timing of anti-CD3 and IL-2 injection are of major importance. Based on these considerations, we propose to administer immunologically active doses of anti-CD3 in vivo to cancer pts. simultaneously with bolus and continuous infusion IL-2. The objectives of this study are: to determine whether anti-CD3 can be safely administered in combination with IL-2; to determine the toxicity of this regimen, to measure selective immunomodulatory effect; to observe any antitumor responses, and determine whether expansion of activated T lymphocytes can be achieved in vivo by this method. Pts. will receive anti-CD3 (400, 800, 1200, & 800 mu/m2), continuous infusion IL-2 (IV- IL2 0.75 mu/m2), and bolus IL-2 (1.5 mu/m2). Cohort 4 will receive cytoxan. 12 pts. have been entered on this study to date. There have been 2 PR's. Pts. have sustained significant toxicity including hypotension, chills, fever, and metabolic acidosis. The hypotension has been more pronounced than with similar doses of IL-2 alone. These have been manageable. We plan to accrue a total of 24 pts.