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低剂量重组白细胞介素-2持续输注联合B细胞特异性单克隆抗体CLB-CD19治疗低度非霍奇金淋巴瘤

Treatment of low-grade non-Hodgkin's lymphoma with continuous infusion of low-dose recombinant interleukin-2 in combination with the B-cell-specific monoclonal antibody CLB-CD19.

作者信息

Vlasveld L T, Hekman A, Vyth-Dreese F A, Melief C J, Sein J J, Voordouw A C, Dellemijn T A, Rankin E M

机构信息

Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam.

出版信息

Cancer Immunol Immunother. 1995 Jan;40(1):37-47. doi: 10.1007/BF01517234.

Abstract

Seven patients with low-grade non-Hodgkin's lymphoma were treated with a combination of a murine monoclonal antibody directed against the B-cell-specific antigen CD19 (CLB-CD19), given twice weekly, and continuous infusion of low-dose recombinant interleukin-2 (rIL-2). We demonstrated stable serum CLB-CD19 levels throughout the 12 weeks of treatment, and homing of the antibody into the tumour sites. A variable degree of antigenic modulation was noted. Prolonged treatment resulted in a sustained increase in the number of natural killer cells in the circulation with enhanced cytotoxic capacity, including antibody-dependent cellular cytotoxicity. During the first weeks of treatment, T cell activation occurred in the majority of patients. Toxicity was related to the rIL-2 treatment and consisted of transient constitutional symptoms and a flu-like syndrome without organ dysfunction. A partial remission occurred in one patient, and in another patient who was primarily leukaemic a greater than 50% reduction of circulating B cells was noted. An antitumour effect occurred early during treatment and could not be related to rIL-2-induced modulation of natural killer cell or T lymphocyte activation.

摘要

七例低度非霍奇金淋巴瘤患者接受了联合治疗,该联合治疗包括每周两次给予一种针对B细胞特异性抗原CD19的鼠单克隆抗体(CLB-CD19),以及持续输注低剂量重组白细胞介素-2(rIL-2)。我们证明在整个12周的治疗过程中血清CLB-CD19水平稳定,且抗体归巢至肿瘤部位。观察到不同程度的抗原调制。延长治疗导致循环中自然杀伤细胞数量持续增加,细胞毒性能力增强,包括抗体依赖性细胞毒性。在治疗的最初几周,大多数患者出现T细胞活化。毒性与rIL-2治疗有关,表现为短暂的全身症状和类似流感的综合征,但无器官功能障碍。一名患者出现部分缓解,另一名主要为白血病的患者循环B细胞减少超过50%。抗肿瘤作用在治疗早期出现,且与rIL-2诱导的自然杀伤细胞或T淋巴细胞活化调制无关。

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