CMC-544 (inotuzumab ozogamicin), an anti-CD22 immuno-conjugate of calicheamicin, alters the levels of target molecules of malignant B-cells
CMC-544 (inotuzumab ozogamicin), an anti-CD22 immuno-conjugate of calicheamicin, alters the levels of target molecules of malignant B-cells
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DOI：
10.1038/leu.2009.77
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发表时间：
2009-07-01
期刊：
影响因子：
11.4
通讯作者：
Ohno, R.
中科院分区：
文献类型：
--
作者：
Takeshita, A.;Yamakage, N.;Ohno, R.
我们研究了 CMC-544（加利车霉素缀合的抗 CD22 单克隆抗体）单独使用以及与利妥昔单抗联合使用的效果，分析了 Daudi 和 Raji 细胞以及从 B 细胞恶性肿瘤 (BCM) 患者获得的细胞中靶分子（即 CD20、CD22、CD55 和 CD59）的定量变化。分别测试了抗体诱导直接抗增殖和凋亡作用、补体依赖性细胞毒性（CDC）和抗体依赖性细胞毒性（ADCC）。在 Daudi 和 Raji 细胞中，与 CMC-544 一起孵育后 12 小时内，利妥昔单抗的 CDC 效果显着增强。与 CMC-544 孵育后，CD22 和 CD55 水平显着降低（两种细胞中 P < 0.001），但 CD20 水平保持恒定或增加 12 小时。在 12 名 BCM 患者的细胞中也获得了类似的结果。 CMC-544的抗增殖和凋亡作用强于利妥昔单抗。 CMC-544 不会增强利妥昔单抗的 ADCC。因此，CMC-544和利妥昔单抗联合使用增加了BCM细胞的体外细胞毒作用，并且CMC-544序贯给药12小时更有效。与 CMC-544 孵育后 CD55 的减少和 CD20 的保留支持了 CMC-544 和利妥昔单抗联合使用的基本原理。白血病 (2009) 23, 1329-1336; doi：10.1038/leu.2009.77； 2009 年 4 月 16 日在线发布
We studied the effect of CMC-544, the calicheamicin-conjugated anti-CD22 monoclonal antibody, used alone and in combination with rituximab, analyzing the quantitative alteration of target molecules, that is, CD20, CD22, CD55 and CD59, in Daudi and Raji cells as well as in cells obtained from patients with B-cell malignancies (BCM). Antibody inducing direct antiproliferative and apoptotic effect, complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) were tested separately. In Daudi and Raji cells, the CDC effect of rituximab significantly increased within 12 h following incubation with CMC-544. The levels of CD22 and CD55 were significantly reduced (P < 0.001 in both cells) after incubation with CMC-544, but CD20 level remained constant or increased for 12 h. Similar results were obtained in cells from 12 patients with BCM. The antiproliferative and apoptotic effect of CMC-544 were greater than that of rituximab. The ADCC of rituximab was not enhanced by CMC-544. Thus, the combination of CMC-544 and rituximab increased the in vitro cytotoxic effect in BCM cells, and sequential administration for 12 h proceeded by CMC-544 was more effective. The reduction of CD55 and the preservation of CD20 after incubation with CMC-544 support the rationale for the combined use of CMC-544 and rituximab. Leukemia (2009) 23, 1329-1336; doi: 10.1038/leu.2009.77; published online 16 April 2009