Robbins D H, Margulies I, Stetler-Stevenson M, Kreitman R J
Laboratory of Clinical Pathology, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
Clin Cancer Res. 2000 Feb;6(2):693-700.
Anti-Tac(Fv)-PE38 (LMB-2) is a recombinant, single-chain immunotoxin composed of the variable domains of the anti-Tac (anti-CD25) monoclonal antibody fused to a truncated form of Pseudomonas exotoxin (PE). Until now, this agent has been reported to be very cytotoxic toward T-cell but not B-cell leukemic cells freshly obtained from patients and is being tested clinically in patients with CD25+ malignancies of both B- and T-cell origin. Hairy cell leukemia (HCL) is a B-cell malignancy in which the cells are usually CD25+ and their ex vivo sensitivity to LMB-2 was unknown. Malignant cells from the first HCL patient to be tested were very sensitive to the cytotoxic effect of LMB-2 in vitro (IC50, 1.1 ng/ml), and this patient responded clinically to LMB-2 administered systemically. Therefore, we decided to assess the potential clinical utility of LMB-2 in other patients with HCL. We tested fresh leukemic cells from nine additional CD25+ HCL patients. LMB-2 was very cytotoxic ex vivo in all patients with IC50s as low as 0.5 ng/ml. Malignant cells freshly obtained from patients with chronic lymphocytic leukemia were also sensitive to LMB-2 but not as sensitive as cells from HCL patients. These results indicate that CD25+ HCL is a B-cell neoplasm that is particularly sensitive to LMB-2, and this agent may be useful in patients who have failed standard therapies.
抗 Tac(Fv)-PE38（LMB-2）是一种重组单链免疫毒素，由抗 Tac（抗 CD25）单克隆抗体的可变区与截短形式的铜绿假单胞菌外毒素（PE）融合而成。到目前为止，据报道该药物对从患者新鲜获取的 T 细胞白血病细胞具有很强的细胞毒性，但对 B 细胞白血病细胞没有毒性，并且正在对 B 细胞和 T 细胞来源的 CD25+恶性肿瘤患者进行临床测试。毛细胞白血病（HCL）是一种 B 细胞恶性肿瘤，其中的细胞通常 CD25+，其对 LMB-2 的体外敏感性尚不清楚。首例接受测试的 HCL 患者的恶性细胞在体外对 LMB-2 的细胞毒性非常敏感（IC50，1.1 ng/ml），并且该患者对全身给药的 LMB-2 有临床反应。因此，我们决定评估 LMB-2 在其他 HCL 患者中的潜在临床应用价值。我们测试了另外 9 例 CD25+ HCL 患者的新鲜白血病细胞。LMB-2 在所有患者的体外均具有很强的细胞毒性，IC50 低至 0.5 ng/ml。从慢性淋巴细胞白血病患者新鲜获取的恶性细胞对 LMB-2 也敏感，但不如 HCL 患者的细胞敏感。这些结果表明，CD25+ HCL 是一种对 LMB-2 特别敏感的 B 细胞肿瘤，并且该药物可能对标准治疗失败的患者有用。
