HUMORAL IMMUNE-RESPONSE TO A RICIN-A CHAIN IMMUNOTOXIN IN PATIENTS WITH METASTATIC MELANOMA
HUMORAL IMMUNE-RESPONSE TO A RICIN-A CHAIN IMMUNOTOXIN IN PATIENTS WITH METASTATIC MELANOMA
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DOI：
10.1089/cdd.1987.4.245
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发表时间：
1987-01-01
期刊：
影响因子：
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通讯作者：
FRANKEL, AE
中科院分区：
文献类型：
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作者：
HERTLER, AA;SPITLER, LE;FRANKEL, AE
免疫毒素是由单克隆抗体与多肽毒素连接而成的杂合分子，在动物模型和早期临床试验中都显示出抗肿瘤活性。然而，它们在治疗人类癌症中的潜在价值可能受到针对缀合物的宿主抗体的开发的限制。这种抗体可能改变免疫毒素的药代动力学和药效学，以及沉淀血清病或过敏反应。使用放射免疫测定法，我们已经测量了一系列的抗蓖麻毒素A链（抗RTA）和抗鼠免疫球蛋白（抗ESTA）滴度在22例患者谁收到的抗黑色素瘤免疫毒素XomaZymeR-Mel。在21例可评价患者中的17例中检测到显著滴度的抗RTA和/或抗IgA。在未产生抗体的4例患者中，2例可能继发于地塞米松、CCNU和地塞米松的免疫抑制。在可检测到抗免疫毒素抗体时接受免疫毒素的2例患者均发生了与免疫介导的过敏反应一致的输注反应。在存在抗RTA时测量血清免疫毒素水平的1例患者中，峰值免疫毒素水平降低。在施用这种设计的免疫毒素的重复过程之前，需要抑制对免疫毒素的人免疫应答的策略。
Immunotoxins, hybrid molecules consisting of a monoclonal antibody linked to a polypeptide toxin have shown anti-tumor activity in both animal models and early clinical trials. However, their potential value in the treatment of human cancer may be limited by the development of host antibodies against the conjugate. Such antibodies could potentially alter immunotoxin pharmacokinetics and pharmacodynamics as well as precipitate serum sickness or anaphylaxis. Using a radioimmunoassay we have measured serial anti-ricin A chain (anti-RTA) and anti-murine immunoglobulin (anti-MIG) titers in 22 patients who received the anti-melanoma immunotoxin XomaZymeR-Mel. Significant titers of anti-RTA and/or anti-MIG were detected in 17 of 21 evaluable patients. Of the four patients not developing antibodies, two were likely immunosuppressed secondary to dexamethasone, and CCNU and dexamethasone respectively. Both patients who received immunotoxin at a time when they had detectable anti-immunotoxin antibodies experienced infusion reactions consistent with immune mediated allergic reponses. There was a decrease in peak immunotoxin level in the one patient who had serum immunotoxin levels measured at a time when anti-RTA was present. Strategies to suppress the human immune response to immunotoxins are required before repetitive courses of immunotoxin of this design may be administered.