PHASE IA/B TRIAL OF ANTICD3 AND INTERLEUKIN 2

LAK细胞和IL-2的初步临床试验与 在约20%的肾病患者中部分或完全缓解 细胞癌和黑素瘤。 然而，抗肿瘤药物的比较 IL-2单独与IL-2与LAK细胞组合的活性显示在 最好只有一个小的临床效益从LAK细胞。 一个最近 在Frederick CRB完成了使用IL-2和体外 抗CD 3活化的T细胞显示出出乎意料的低应答率。 这项试验的一个局限性是， 在外周血中循环的细胞可以被激活。 临床前研究 这表明，在CD 8+细胞是排斥模式的肿瘤中， 抗-CD 3和IL-2注射的时机是非常重要的。 基于 考虑到这些因素，我们建议给予免疫活性 剂量的抗-CD 3在体内给癌症患者。与推注同时进行， 持续输注IL-2。 本研究的目的是：确定 抗CD 3是否可以与IL-2联合安全给药; 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淋巴细胞的扩增是否可以在体内通过 该方法 重量份将接受抗CD 3（400、800、1200和800 mu/m2）， 连续输注IL-2（IV-IL-20.75 μ/m2）和推注IL-2（1.5 μ/m2）。 队列4将接受环磷酰胺。 12分。已进入本研究， 约会 有两个PR。 重量份具有持续的显著毒性 包括低血压、寒战、发热和代谢性酸中毒。 的 低血压比类似剂量的IL-2更明显 一个人 这些都是可控的。 我们计划累计24个百分点。

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.