Mischak R P, Foxall C, Rosendorf L L, Knebel K, Scannon P J, Spitler L E
XOMA Corporation, Berkeley, CA.
Mol Biother. 1990 Jun;2(2):104-9.
Human antibody responses to immunotoxin components were evaluated in 21 melanoma patients who were treated with XomaZyme-MEL, a murine monoclonal antimelanoma antibody-ricin A chain conjugate. Twenty of the 21 melanoma patients produced antibodies against ricin A chain, while 15 of 21 produced antibodies reactive with the murine monoclonal antibody component. Both IgM and IgG antibody responses were produced. Immunoglobulin responses were usually detected 1 to 2 weeks following initiation of therapy, with peak levels generally attained 2 to 4 weeks posttherapy. Titers of the anti-ricin A chain antibodies were generally higher than those of the antimurine monoclonal antibodies for the dose range tested. There was no clear correlation between the dose of immunotoxin administered and the antibody titer. By use of a competitive flow cytometry assay, antiidiotype responses were demonstrated in eight of 10 melanoma patients who had antimurine antibodies. Both the kinetics of appearance and the relative titers of the antiidiotype responses generally corresponded to the antimurine responses. The development of antimmunotoxin antibodies can reduce the therapeutic potential of immunotoxins through several mechanisms. The development of antibodies in a significant number of patients suggests that optimally effective, repeated courses of therapy will require some procedure for suppressing or abrogating the response against the immunotoxin.
在21例接受XomaZyme-MEL（一种鼠单克隆抗黑色素瘤抗体-蓖麻毒素A链偶联物）治疗的黑色素瘤患者中，评估了人体对免疫毒素成分的抗体反应。21例黑色素瘤患者中有20例产生了针对蓖麻毒素A链的抗体，21例中有15例产生了与鼠单克隆抗体成分反应的抗体。IgM和IgG抗体反应均有产生。免疫球蛋白反应通常在治疗开始后1至2周检测到，峰值水平一般在治疗后2至4周达到。在所测试的剂量范围内，抗蓖麻毒素A链抗体的滴度通常高于抗鼠单克隆抗体的滴度。给予的免疫毒素剂量与抗体滴度之间没有明显的相关性。通过竞争性流式细胞术检测，在10例有抗鼠抗体的黑色素瘤患者中有8例表现出抗独特型反应。抗独特型反应的出现动力学和相对滴度通常与抗鼠反应一致。抗免疫毒素抗体的产生可通过多种机制降低免疫毒素的治疗潜力。大量患者产生抗体表明，最佳有效的重复治疗疗程将需要某种抑制或消除针对免疫毒素反应的程序。
