Petersen B H, DeHerdt S V, Schneck D W, Bumol T F
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46202.
Cancer Res. 1991 May 1;51(9):2286-90.
Monoclonal antibody (MoAb) conjugates have been used to treat a variety of malignancies. The majority of the MoAbs which have been used therapeutically are from murine sources. The infusion of these foreign proteins into humans can be expected to elicit anti-murine antibodies and may be one of the major limitations to the clinical use of murine MoAbs. In these studies, we report on the nature and specificity of the human anti-murine antibody (HAMA) response in patients given single and multiple infusions of the two Vinca alkaloid conjugates of the MoAb KS1/4, which recognizes tumor-associated antigens in a variety of adenocarcinomas. A HAMA response was induced in a majority of the patients receiving infusions of KS1/4 conjugates, regardless of the specific conjugate used or the number of infusions. The magnitude of the response did not appear to be dose related. Antibodies directed to the drug moieties of these conjugates, anti-Vinca alkaloids, were also induced in patients with HAMA responses. The magnitude of the anti-Vinca response paralleled that of the HAMA.
单克隆抗体（MoAb）偶联物已被用于治疗多种恶性肿瘤。大多数用于治疗的单克隆抗体来源于鼠类。将这些外源蛋白注入人体预计会引发抗鼠抗体，这可能是鼠源单克隆抗体临床应用的主要限制之一。在这些研究中，我们报告了接受单次和多次注射MoAb KS1/4的两种长春花生物碱偶联物的患者中，人抗鼠抗体（HAMA）反应的性质和特异性，该抗体可识别多种腺癌中的肿瘤相关抗原。无论使用的具体偶联物或注射次数如何，大多数接受KS1/4偶联物注射的患者都会诱导出HAMA反应。反应的强度似乎与剂量无关。在出现HAMA反应的患者中也诱导出了针对这些偶联物药物部分的抗体，即抗长春花生物碱抗体。抗长春花反应的强度与HAMA反应的强度相似。
