Chimeric anti-CD20 (IDEC-C2B8) monoclonal antibody sensitizes a B cell lymphoma cell line to cell killing by cytotoxic drugs
Chimeric anti-CD20 (IDEC-C2B8) monoclonal antibody sensitizes a B cell lymphoma cell line to cell killing by cytotoxic drugs
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DOI：
10.1089/cbr.1997.12.177
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发表时间：
1997-01-01
影响因子：
3.4
通讯作者：
Bonavida, B
中科院分区：
文献类型：
--
作者：
Demidem, A;Lam, T;Bonavida, B
超过50%的侵袭性B淋巴瘤患者和大多数低度恶性淋巴瘤患者不能通过目前的治疗策略治愈。淋巴瘤在细胞表面表达B细胞抗原CD 20，该抗原用作抗体导向疗法的靶点。使用嵌合抗CD 20抗体（IDEC-C2 B8）进行的临床研究结果令人鼓舞，该抗体由鼠单克隆抗CD 20抗体IDEC-2B 8的人IgG 1 -6恒定区和可变区组成。本研究调查了抗C2 B8和细胞毒性药物联合治疗的潜在抗肿瘤治疗价值。体外研究检查了C2 B8抗体对DHL-4 B淋巴瘤细胞系对各种细胞毒性药物的致敏作用。通过MTT测定法测定细胞毒性。通过流式细胞术测定表面和细胞质蛋白。用C2 B8预处理DHL-4导致细胞增殖抑制和细胞死亡，并且一部分细胞发生凋亡。虽然DHL-4肿瘤细胞对几种细胞毒性药物具有相对抗性，但用C2 B8预处理使细胞对TNF-α蓖麻毒素、白喉毒素（DTX）、阿霉素和顺铂敏感，但对VP-16不敏感。DHL-4肿瘤细胞的化疗敏感性不是由于MDR-1或bcl-2基因产物的下调。然而，用C2 B8处理DHL-4抑制TNF-α分泌。这些发现表明C2 B8抗体增强DHL-4肿瘤细胞对几种细胞毒性剂的敏感性。此外，研究结果表明，C2 B8抗体和药物的联合治疗可能在治疗耐药侵袭性B淋巴瘤患者中具有临床益处。
More than 50% of patients with aggressive B lymphomas and the majority of patients with low grade lymphomas are not cured by current therapeutic strategies. The lymphomas express the B cell antigen CD20 on the cell surface and this antigen serves as target for antibody-directed therapies. Clinical studies with encouraging results have been underway with the use of a chimeric anti-CD20 antibody (IDEC-C2B8), consisting of human IgG1-6 constant regions and variable regions from the murine monoclonal anti-CD20 antibody IDEC-2B8. this study investigated the potential anti-tumor therapeutic value of combination treatment with anti-C2B8 and cytotoxic drugs. The in vitro study examined the sensitizing effect of C2B8 antibody on the DHL-4 B lymphoma line to various cytotoxic agents. Cytotoxicity was determined by, the MTT assay. Surface and cytoplasmic proteins were determined by flow cytometry. Pretreatment of DHL-4 with C2B8 resulted in inhibition of cell proliferation and cell death and a fraction of the cells underwent apoptosis. While the DHL-4 tumor cells were relatively resistant to several cytotoxic drugs, pretreatment with C2B8 rendered the cells sensitive to TNF-alpha ricin, diphtheria toxin (DTX), adriamycin and cisplatin but not to VP-16. Chemosensitization of DHL-4 tumor cells was not due to downmodulation of either the MDR-1 or bcl-2 gene products. However, treatment of DHL-4 with C2B8 inhibited TNF-alpha secretion. These findings demonstrate that C2B8 antibody, potentiates the sensitivity of DHL-4 tumor cells to several cytotoxic agents. Further, the findings suggest that combination treatments with C2B8 antibody and drugs may be of clinical benefit in the treatment of patients with resistant aggressive B lymphomas.