Treon Steven P, Kelliher Abigail, Keele Beverly, Frankel Stanley, Emmanouilides Christos, Kimby Eva, Schlossman Robert, Mitsiades Nicholas, Mitsiades Constantine, Preffer Frederic, Anderson Kenneth C
Dana Farber Cancer Institute, Massachusetts General Hospital, Harvard Medical School, Boston 02115, USA.
Semin Oncol. 2003 Apr;30(2):248-52. doi: 10.1053/sonc.2003.50047.
Monoclonal antibody (mAb) therapy (serotherapy) has been successfully used in the treatment of many B-cell malignancies, among them lymphoplasmacytic lymphoma, an uncommon disorder that includes patients with the clinicopathological diagnosis of Waldenstrom's macroglobulinemia (WM). Rituximab, a mAb directed at CD20, was recently demonstrated by us and others to induce remissions and facilitate hematological recovery in patients with WM. The expression of CD20, along with targets of other mAbs which are commercially available, currently in clinical trials, or in preclinical development, have not been extensively studied or well documented in lymphoplasmacytic lymphoma. As such, we examined by flow cytometric analysis tumor cells from a large series of patients with the histopathlogical diagnosis of lymphoplasmacytic lymphoma and the clinicopathological diagnosis of WM for expression of the serotherapy target antigens CD20, CD22, CD40, CD52, IgM, MUC1 core protein, and 1D10. These studies demonstrated antigen expression on >or=50% of bone marrow tumor cells (CD19(+), kappa/lambda light chain-restricted), respectively, from patients as follows: CD20 (98.3%), CD22 (88.3%), CD40 (83.3%), CD52 (77.4%), IgM (83.3%), MUC1 core protein (57.8%), and 1D10 (50%). Both interpatient and intrapatient tumor clone antigen expression was heterogeneous. Combined mAb therapy might be a useful approach to cope with this variation, and could be tailored to target all members of the tumor clone for an individual patient.
单克隆抗体（mAb）疗法（血清疗法）已成功用于治疗多种B细胞恶性肿瘤，其中包括淋巴浆细胞淋巴瘤，这是一种罕见的疾病，包括经临床病理诊断为华氏巨球蛋白血症（WM）的患者。利妥昔单抗是一种针对CD20的单克隆抗体，最近我们和其他人证明它能诱导WM患者缓解并促进血液学恢复。CD20以及其他市售、目前正在临床试验或临床前开发的单克隆抗体的靶点在淋巴浆细胞淋巴瘤中的表达尚未得到广泛研究或充分记录。因此，我们通过流式细胞术分析了一系列经组织病理学诊断为淋巴浆细胞淋巴瘤且经临床病理诊断为WM的患者的肿瘤细胞，以检测血清疗法靶抗原CD20、CD22、CD40、CD52、IgM、MUC1核心蛋白和1D10的表达。这些研究表明，以下患者骨髓肿瘤细胞（CD19(+)，κ/λ轻链受限）中分别有≥50%表达抗原：CD20（98.3%）、CD22（88.3%）、CD40（83.3%）、CD52（77.4%）、IgM（83.3%）、MUC1核心蛋白（57.8%）和1D10（50%）。患者间和患者内肿瘤克隆的抗原表达均存在异质性。联合单克隆抗体疗法可能是应对这种变异的一种有用方法，并且可以针对个体患者的肿瘤克隆所有成员进行定制。
