Nadler L M, Stashenko P, Hardy R, Kaplan W D, Button L N, Kufe D W, Antman K H, Schlossman S F
Cancer Res. 1980 Sep;40(9):3147-54.
A preliminary serotherapeutic trial was undertaken with a monoclonal antibody designated antibody 89 (Ab 89) directed against a lymphoma-associated antigen. In vitro studies demonstrated that Ab 89 could mediate complement-dependent lysis and macrophage adherence but not antibody-dependent cell-mediated cytotoxicity. To evaluate toxicity and therapeutic efficacy, two courses of Ab 89 were administered to a patient with an Ab 89-reactive tumor. Transient decreases in the number of circulating tumor cells and the appearance of circulating dead cells were noted with the infusion of Ab 89. Following administration of 150 mg or more of Ab 89, small amounts of antibody could be demonstrated on circulating tumor cells at a time when no free antibody was found in the serum. The inability to deliver a significant amount of Ab 89 to tumor cells in vivo is thought to be secondary to a circulating tumor antigen. Following each infusion, the amount of this blocking antigen decreased but could not be entirely cleared from the serum. This study provides preliminary evidence for the lack of clinical toxicity of a monoclonal antibody and identifies circulating blocking antigens as a significant obstacle to serotherapy.
开展了一项初步的血清治疗试验,使用一种针对淋巴瘤相关抗原的单克隆抗体,即抗体89(Ab 89)。体外研究表明,Ab 89可介导补体依赖性细胞溶解和巨噬细胞黏附,但不能介导抗体依赖性细胞介导的细胞毒性。为评估毒性和治疗效果,对一名患有Ab 89反应性肿瘤的患者给予了两个疗程的Ab 89。输注Ab 89时,观察到循环肿瘤细胞数量短暂减少以及循环死细胞出现。给予150 mg或更多的Ab 89后,在血清中未发现游离抗体时,可在循环肿瘤细胞上检测到少量抗体。体内无法将大量Ab 89递送至肿瘤细胞被认为是循环肿瘤抗原所致。每次输注后,这种阻断抗原的量会减少,但无法从血清中完全清除。这项研究为单克隆抗体缺乏临床毒性提供了初步证据,并确定循环阻断抗原是血清治疗的一个重大障碍。