Laboratory of Molecular Biology, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Sci Transl Med. 2013 Oct 23;5(208):208ra147. doi: 10.1126/scitranslmed.3006941.
Immunotoxins are potent anticancer agents with an unusual mechanism of action: inhibition of protein synthesis resulting in apoptotic cell death. Immunotoxins have produced many durable complete responses in refractory hairy cell leukemia, where patients rarely form antibodies to the bacterial toxin component of the immunotoxin. Patients with mesothelioma, however, have normal immune systems and form antibodies after one cycle, and tumor responses to the immunotoxin have not been observed in this disease. We describe the results of a trial in which major antitumor responses were seen in patients with advanced mesothelioma who received the anti-mesothelin immunotoxin SS1P, together with pentostatin and cyclophosphamide, to deplete T and B cells. Of 10 patients with chemotherapy-refractory mesothelioma, 3 have had major tumor regressions with 2 ongoing at 15 months, and 2 others responded to chemotherapy after discontinuing immunotoxin therapy. Antibody formation was markedly delayed, allowing more SS1P cycles to be given, but this alone does not appear to account for the marked antitumor activity observed.
抑制蛋白质合成导致细胞凋亡。免疫毒素在难治性毛细胞白血病中产生了许多持久的完全缓解，在这些患者中，很少对免疫毒素的细菌毒素成分产生抗体。然而，间皮瘤患者的免疫系统正常，在一个周期后会产生抗体，并且在这种疾病中没有观察到免疫毒素对肿瘤的反应。我们描述了一项试验的结果，在该试验中，接受抗间皮素免疫毒素 SS1P 联合戊柔比星和环磷酰胺治疗以耗尽 T 和 B 细胞的晚期间皮瘤患者中出现了主要的抗肿瘤反应。在 10 名化疗耐药性间皮瘤患者中，3 名患者的肿瘤有明显消退，其中 2 名患者持续 15 个月，另外 2 名患者在停止免疫毒素治疗后对化疗有反应。抗体形成明显延迟，允许给予更多的 SS1P 周期，但这似乎并不能完全解释所观察到的显著抗肿瘤活性。
