EUFETS GmbH, Idar-Oberstein, Germany.
Clin Transl Oncol. 2011 Dec;13(12):889-98. doi: 10.1007/s12094-011-0751-5.
BACKGROUND Trifunctional antibodies, such as catumaxomab (anti-EpCAM×anti-CD3) and ertumaxomab (anti- HER-2/neu×anti-CD3), transiently link immune effector cells to tumour cells, which results in cellular cytotoxicity towards the tumour cells. A functional immune system is therefore essential for effective anti-tumour activity. However, the commonly observed haematotoxicity of chemotherapeutics and radiation therapy may be associated with some degree of immunosuppression. Combining chemotherapy and trifunctional antibodies in cancer treatment requires understanding of the impact of chemotherapeutics on immune cell function and, thus, on the activity of trifunctional antibodies. METHODS The effect of chemotherapeutic treatment on trifunctional antibody-mediated anti-tumour activity was assessed in vitro. Blood samples were collected from 12 head and neck squamous cell carcinoma patients after chemotherapy (5-fluorouracil, cisplatin) and radiotherapy, and from one healthy control donor. The immune cell status was analysed and mononuclear cells (MNC) were isolated. The potency of catumaxomab and ertumaxomab was assessed in a cytotoxicity assay using MNC isolated from each patient sample in co-culture with a tumour target cell line. The release of infl ammatory cytokines was also monitored in the cell culture supernatant. RESULTS Most patients included in this study had decreased immune cell counts during the course of chemotherapy. Nonetheless, an effective and concentration-dependent anti- tumour activity mediated by trifunctional antibodies was demonstrated using these patient immune effector cells. The immune response activity of the patient immune cells was not impaired one week after cisplatin administration or even three days after the last 5-fluorouracil treatment. CONCLUSION This study shows for the first time that immune effector cells from cancer patients undergoing standard chemotherapy and radiotherapy can be activated by trifunctional antibodies for efficient killing of tumour cells.
三功能抗体，如 catumaxomab（抗-EpCAM×抗-CD3）和 ertumaxomab（抗-HER-2/neu×抗-CD3），可将免疫效应细胞短暂连接到肿瘤细胞上，从而导致对肿瘤细胞的细胞毒性。因此，功能正常的免疫系统对于有效的抗肿瘤活性是必不可少的。然而，化疗药物和放射治疗通常观察到的血液毒性可能与一定程度的免疫抑制有关。在癌症治疗中结合化疗和三功能抗体需要了解化疗药物对免疫细胞功能的影响，进而影响三功能抗体的活性。
在体外评估化疗治疗对三功能抗体介导的抗肿瘤活性的影响。从接受化疗（5-氟尿嘧啶、顺铂）和放疗的 12 例头颈部鳞状细胞癌患者和 1 名健康对照供体中采集血液样本。分析免疫细胞状态并分离单核细胞（MNC）。使用从每个患者样本中分离的 MNC 与肿瘤靶细胞系共培养，在细胞毒性测定中评估 catumaxomab 和 ertumaxomab 的效力。还监测细胞培养上清液中炎症细胞因子的释放。
本研究中大多数患者在化疗过程中免疫细胞计数减少。尽管如此，使用这些患者免疫效应细胞证明了三功能抗体介导的有效且浓度依赖性的抗肿瘤活性。患者免疫细胞的免疫反应活性在顺铂给药后一周甚至在最后一次 5-氟尿嘧啶治疗后三天都没有受损。
这项研究首次表明，接受标准化疗和放疗的癌症患者的免疫效应细胞可以被三功能抗体激活，从而有效地杀死肿瘤细胞。
