IMMUNOTOXIN PROTOCOLS

A.持续输液联合治疗的第一阶段中试研究 免疫毒素Ig G-RFB4-SMPT-DGA联合Ig G-HD37-SMPT-DGA治疗难治性CD19+ CD22+B细胞淋巴瘤。这项研究建立在先前的经验基础上 各自的免疫毒素被用作单一试剂，并试图确定 鸡尾酒的安全性一起服用，以及寻求 获得一些疗效的初步证据。两个剂量级别(5和10 到目前为止，已经研究了每种毒素的mg/M2/192小时。有首字母 有证据表明，MTD会因是否存在循环肿瘤而不同 细胞已经很明显了。三个没有循环肿瘤的患者中有两个 细胞在较高剂量水平下出现III级毒性，而 3例循环肿瘤细胞患者无一例出现III级 毒性或更大。已经获得了初步证据，在相同的情况下 患者对免疫毒素的处理根据患者的不同而不同 目的抗原的表达。 B.与免疫毒素和未结合抗体的相关性研究。在……里面 确定生长发育关系的相关实验室研究 肿瘤细胞株对靶抗原表达的抑制作用 和临床药理学的比较，我们观察到HD37抗体 在某些方面与抗增殖剂一样有效 Ig G-HD37-SMPT-DGA免疫毒素。该抗体导致G1期停滞和 PRb的低磷酸化。这些结果表明，经济的负增长 抗体的调节作用可补充其细胞毒作用 联合治疗中的一种免疫毒素。

A. A Pilot Phase I Study of Combination Therapy with Continuous Infusion Immunotoxins IgG-RFB4-SMPT-dgA plus IgG-HD37-SMPT-dgA in Refractory CD19+, CD22+ B cell Lymphoma. This study builds on the prior experience with the respective immunotoxins utilized as single agents and seeks to determine the safety of the cocktail administered together as well as seeking to obtain some initial evidence of efficacy. Two dose levels(5 and 10 mg/M2/192 hr of each toxin have been thus far studied. There is initial evidence that the MTD will differ depending on whether circulating tumor cells are in evidence. Two of three patients without circulating tumor cells experienced Grade III toxicity at the higher dose level, whereas none of three patients with circulating tumor cells experienced Grade III toxicity or greater. Initial evidence has been obtained that in the same patient the handling of the immunotoxins differed depending on the expression of the target antigens. B. Correlative studies with Immunotoxins and Unconjugated Antibodies. In correlative laboratory studies to determine the relation of growth inhibition in tumor cell lines to the expression of the target antigens and clinical pharmacology of the agents, we observed that HD37 antibody was as effective in some respects as an antiproliferative agent as the IgG-HD37-SMPT-dgA immunotoxin. The antibody caused G1 arrest and hypophosphorylation of pRb. These results suggest that the negative growth regulatory effects of an antibody may complement the cytotoxic action of an immunotoxin in combined approaches.