Heuck Friederike, Ellermann Julia, Borchmann Peter, Rothe Achim, Hansen Hinrich, Engert Andreas, von Strandmann Elke Pogge
Laboratory of Immunotherapy, Department I for Internal Medicine, University Hospital Cologne, Cologne, Germany.
J Immunother. 2004 Sep-Oct;27(5):347-53. doi: 10.1097/00002371-200409000-00003.
Due to its selective overexpression on the malignant cells of Hodgkin's lymphoma (HL) and large cell anaplastic lymphoma (ALCL), CD30 is an excellent target for immunotherapy of these diseases. The fully human monoclonal anti-CD30-antibody 5F11 has been shown to be effective against CD30-expressing cell lines both in vitro and in vivo. In addition, 5F11 shows promising antitumor activity in phase 1/2 clinical trials. To extend these promising results, the authors evaluated combinations of 5F11 with conventional cytostatic drugs against a variety of lymphoma cell lines in vitro. Most combinations tested showed at least additive cytotoxic effects on the HL-derived cell lines L428, L540, and L1236 and the ALCL-derived cell line Karpas 299 as measured by proliferation assays (XTT) and the induction of apoptosis (annexin-V FACS analysis). The most impressive results were detected with the combination of 5F11 and gemcitabine or etoposide. The data suggest that the combination of the human antibody 5F11 with conventional chemotherapy might be beneficial in the combined chemo-immunotherapy of CD30-positive lymphomas.
由于CD30在霍奇金淋巴瘤(HL)和间变性大细胞淋巴瘤(ALCL)的恶性细胞上选择性过表达,它是这些疾病免疫治疗的理想靶点。完全人源化单克隆抗CD30抗体5F11已被证明在体外和体内对表达CD30的细胞系均有效。此外,5F11在1/2期临床试验中显示出有前景的抗肿瘤活性。为了扩展这些有前景的结果,作者在体外评估了5F11与传统细胞毒性药物联合对多种淋巴瘤细胞系的作用。通过增殖试验(XTT)和凋亡诱导(膜联蛋白-V流式细胞术分析)测定,大多数测试的联合用药对HL来源的细胞系L428、L540和L1236以及ALCL来源的细胞系Karpas 299均显示出至少相加的细胞毒性作用。5F11与吉西他滨或依托泊苷联合用药检测到了最显著的结果。数据表明,人源抗体5F11与传统化疗联合可能对CD30阳性淋巴瘤的联合化疗免疫治疗有益。