Antimelanoma monoclonal antibody-ricin A chain immunoconjugate (XMMME-001-RTA) plus cyclophosphamide in the treatment of metastatic malignant melanoma: results of a phase II trial.

R Oratz, J L Speyer, J C Wernz, H Hochster, M Meyers, R Mischak, L E Spitler
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Abstract

Prior studies with the XMMME-001-RTA immunoconjugate composed of an antimelanoma monoclonal antibody and ricin A chain demonstrated some antitumor activity. However, almost all patients studied developed human antimurine antibodies and antiricin antibodies. In an effort to abrogate these host anti-immunotoxin immune responses and thus enhance antitumor activity, we treated 20 patients with the immunoconjugate plus a single dose of intravenous cyclophosphamide. An overall response rate of 20% was observed-predominantly in pulmonary and soft tissue nodules. There was no diminution in antibody responses against either the murine antibody or the ricin moiety. Further studies to elucidate the role of cyclophosphamide in monoclonal antibody therapy are planned.

抗黑色素瘤单克隆抗体-蓖麻毒素A链免疫偶联物(XMMME-001-RTA)加环磷酰胺治疗转移性恶性黑色素瘤:一项II期试验的结果
先前的研究表明,由抗黑色素瘤单克隆抗体和蓖麻毒素A链组成的XMMME-001-RTA免疫偶联物具有一定的抗肿瘤活性。然而,几乎所有研究的患者都产生了人类抗尿抗体和抗蓖麻毒素抗体。为了消除这些宿主抗免疫毒素免疫反应,从而增强抗肿瘤活性,我们用免疫偶联物加单剂量静脉注射环磷酰胺治疗了20例患者。观察到总有效率为20%,主要是肺和软组织结节。对小鼠抗体或蓖麻毒素片段的抗体反应没有减少。我们计划进一步研究环磷酰胺在单克隆抗体治疗中的作用。
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