Ciavarella D
Department of Clinical Pathology, New York Medical College, Valhalla 10595.
Int J Clin Lab Res. 1992;21(3):210-3. doi: 10.1007/BF02591648.
The staphylococcal cell-wall protein known as protein A has been explored as a therapeutic modality in the treatment of cancer and allied diseases. Protein A binds the Fc fragment of IgG 1, 2 and 4, and preferentially binds to IgG incorporated into immune complexes. Early investigators focused on the immune-suppressive effects of immune complexes in cancer and, based on in vitro experiments, postulated that clearance of immune complexes in vivo would permit effective immune clearance of cancer cells. A large clinical trial of the perfusion of cancer patient plasma over protein A was subsequently undertaken. Results were generally disappointing, with no complete remissions and overall response rates of 22%. Response rates for Kaposi's sarcoma (39%) and breast adenocarcinoma (26%) were somewhat encouraging, and further clinical trials in these disorders are ongoing. More impressive have been the responses to protein A perfusion in immune thrombocytopenia and hemolytic-uremic syndrome. Using a protein A-silica device, Snyder et al. reported responses in 42% of immune thrombocytopenia patients, with mean increases in platelet count from 27 x 10(9)/l to 120 x 10(9)/l. On the basis of these results, the protein A-silica column was approved by the United States Food and Drug Administration for treatment of immune thrombocytopenia. Equally encouraging are reports of an overall 59% response rate in cancer chemotherapy-related hemolytic-uremic syndrome. Reported toxicities include fever, chills, hypotension, dyspnea and musculoskeletal pain. With rare exceptions, these reactions are easily treated and do not result in cessation of therapy. Unfortunately, the mechanism of action of plasma perfusion over protein A is very unclear.(ABSTRACT TRUNCATED AT 250 WORDS)
被称为蛋白A的葡萄球菌细胞壁蛋白已被探索作为治疗癌症及相关疾病的一种治疗方式。蛋白A可结合IgG 1、2和4的Fc片段,并优先结合并入免疫复合物中的IgG。早期研究者关注免疫复合物在癌症中的免疫抑制作用,并基于体外实验推测,体内免疫复合物的清除将允许对癌细胞进行有效的免疫清除。随后开展了一项关于用蛋白A灌注癌症患者血浆的大型临床试验。结果总体令人失望,没有完全缓解,总体缓解率为22%。卡波西肉瘤(39%)和乳腺腺癌(26%)的缓解率有些令人鼓舞,针对这些疾病的进一步临床试验正在进行。在免疫性血小板减少症和溶血尿毒综合征中,蛋白A灌注的反应更令人印象深刻。使用蛋白A-硅胶装置,斯奈德等人报告称,42%的免疫性血小板减少症患者有反应,血小板计数平均从27×10⁹/L增加到120×10⁹/L。基于这些结果,蛋白A-硅胶柱被美国食品药品监督管理局批准用于治疗免疫性血小板减少症。同样令人鼓舞的是,癌症化疗相关溶血尿毒综合征的总体反应率报告为59%。报告的毒性包括发热、寒战、低血压、呼吸困难和肌肉骨骼疼痛。除极少数情况外,这些反应易于治疗,不会导致治疗中断。不幸的是,蛋白A血浆灌注的作用机制非常不清楚。(摘要截短于250词)