Carlo-Stella Carmelo, Guidetti Anna, Di Nicola Massimo, Longoni Paolo, Cleris Loredana, Lavazza Cristiana, Milanesi Marco, Milani Raffaella, Carrabba Matteo, Farina Lucia, Formelli Franca, Gianni Alessandro M, Corradini Paolo
Cristina Gandini Medical Oncology Unit, Istituto Nazionale Tumori, Milano, Italy.
Exp Hematol. 2006 Jun;34(6):721-7. doi: 10.1016/j.exphem.2006.03.005.
To explore new treatments specifically targeting malignant plasma cells (PCs), we examined CD52 antigen expression on primary PCs as well as multiple myeloma (MM) cell lines, and investigated in vivo the antimyeloma activity of alemtuzumab.
PCs were enriched from the marrow of MM patients (n = 39) according to CD138 expression and then analyzed by 3-color flow cytometry and quantitative PCR. The in vivo activity of alemtuzumab was evaluated in a xenotransplant model of MM in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice.
CD52 expression revealed a substantial heterogeneity in terms of both percentage of positive cells and fluorescence intensity, with 25/39 (64%) MM patients showing >or=30% CD138(+) PCs expressing the CD52 antigen (mean = 79%; range, 33-100%). Similarly to primary cells, cell lines showed heterogeneous CD52 expression. Expression of CD52 mRNA by quantitative PCR analysis strongly correlated with CD52 antigen detection by flow cytometry. In vivo, alemtuzumab treatment significantly increased the median survival of animals with an early- (64 vs 77 days, p <or= 0.0005) or advanced-stage (66 vs 75 days, p <or= 0.02) disease.
We conclude that: 1) CD52 is expressed on PCs of a significant proportion of MM patients; 2) alemtuzumab used as a single agent exerts a good antitumor activity in NOD/SCID mice bearing an early-stage disease; and 3) alemtuzumab might have therapeutic potential in a subset of MM patients.
为探索特异性靶向恶性浆细胞（PCs）的新治疗方法，我们检测了原发性PCs以及多发性骨髓瘤（MM）细胞系上CD52抗原的表达，并在体内研究了阿仑单抗的抗骨髓瘤活性。
根据CD138表达情况从MM患者（n = 39）的骨髓中富集PCs，然后通过三色流式细胞术和定量PCR进行分析。在非肥胖糖尿病/严重联合免疫缺陷（NOD/SCID）小鼠的MM异种移植模型中评估阿仑单抗的体内活性。
CD52表达在阳性细胞百分比和荧光强度方面均显示出显著的异质性，25/39（64%）的MM患者显示≥30%的CD138(+) PCs表达CD52抗原（平均 = 79%；范围，33 - 100%）。与原代细胞相似，细胞系也显示出异质性的CD52表达。通过定量PCR分析检测到的CD52 mRNA表达与通过流式细胞术检测到的CD52抗原表达密切相关。在体内，阿仑单抗治疗显著提高了早期（64天对77天，p≤0.0005）或晚期（66天对75天，p≤0.02）疾病动物的中位生存期。
我们得出以下结论：1）相当比例的MM患者的PCs表达CD52；2）阿仑单抗作为单一药物在患有早期疾病的NOD/SCID小鼠中具有良好的抗肿瘤活性；3）阿仑单抗可能对一部分MM患者具有治疗潜力。
