Fierlbeck G, Schreiner T, Schaber B, Walser A, Rassner G
Department of Dermatology, University of Tübingen, Germany.
Cancer Immunol Immunother. 1994 Oct;39(4):263-8. doi: 10.1007/BF01525990.
The incidence and clinical significance of therapy-induced neutralizing interferon beta (IFN beta) antibodies was studied in a group of 21 melanoma patients treated with natural IFN beta and 7 patients treated with recombinant IFN beta. They were treated subcutaneously with 3 x 10(6) IU three times per week in an adjuvant open trial for 24 weeks after surgical removal of all detectable metastases. Of the 21 patients treated with natural IFN beta, 95% developed significant levels of neutralizing antibodies after 24 weeks. In comparison, 28% of the 7 patients treated with recombinant IFN beta developed neutralizing IFN beta antibodies. Cross-reactivity of the antibodies could be demonstrated. Persistence of antibody titers was seen in 80% of the patients 24 weeks after cessation of treatment with natural IFN beta. No correlation between the maximum antibody titers and the antibody persistence after cessation of therapy could be established. We detected a clear correlation between the formation of neutralizing antibodies and the decrease in beta 2-microglobulin and 2',5'-oligoadenylate synthetase and therefore the drop in biological activity. In this adjuvant trial there was no difference in relapse rate and time until relapse between antibody-positive and antibody-negative patients. No difference in clinical outcome could be established between the patients treated with natural IFN beta and recombinant IFN beta.
在一组接受天然干扰素β治疗的21例黑色素瘤患者和7例接受重组干扰素β治疗的患者中，研究了治疗诱导的中和性干扰素β（IFNβ）抗体的发生率及其临床意义。在手术切除所有可检测到的转移灶后，他们在一项辅助开放性试验中接受皮下注射，剂量为3×10⁶IU，每周3次，持续24周。在接受天然干扰素β治疗的21例患者中，95%在24周后产生了显著水平的中和抗体。相比之下，接受重组干扰素β治疗的7例患者中有28%产生了中和性IFNβ抗体。抗体的交叉反应性得到了证实。在停止使用天然干扰素β治疗24周后，80%的患者抗体滴度持续存在。治疗停止后，最大抗体滴度与抗体持续存在之间未发现相关性。我们检测到中和抗体的形成与β2-微球蛋白和2',5'-寡腺苷酸合成酶的降低以及生物活性的下降之间存在明显相关性。在这项辅助试验中，抗体阳性和抗体阴性患者之间的复发率和复发时间没有差异。接受天然干扰素β治疗的患者与接受重组干扰素β治疗的患者在临床结局上没有差异。
