Production of neutralizing granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) antibodies in carcinoma patients following GM‐CSF combination therapy
Production of neutralizing granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) antibodies in carcinoma patients following GM‐CSF combination therapy
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GM-CSF 联合治疗后癌症患者中中和粒细胞-巨噬细胞集落刺激因子 (GM-CSF) 抗体的产生
DOI：
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发表时间：
1996
影响因子：
4.6
通讯作者：
R. Thorpe
中科院分区：
文献类型：
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作者：
M. Wadhwa;C. Bird;J. Fagerberg;Rose Gaines;P. Ragnhammar;Håkan Mellstedt;R. Thorpe
在本研究中，在20例接受大肠埃希菌源性GM-CSF和结肠癌反应性MoAb联合治疗的转移性结直肠癌患者中分析了中和和非中和GM-CSF抗体的产生以及与这些抗体诱导相关的临床后果，这些患者未接受任何伴随化疗。皮下注射重组人GM-CSF，每月10天，持续4个月。在第一个治疗周期后，未检测到GM-CSF抗体，但在随后的治疗中，20例患者中有19例出现了GM-CSF结合抗体。然而，在体外生物测定中，19例抗体阳性患者中只有一部分（40%）产生了中和GM-CSF生物活性的抗体。GM-CSF中和抗体的存在与GM-CSF诱导的白细胞、中性粒细胞和嗜酸性粒细胞扩增的显着减少相关。在非中和抗体患者中，此类临床效应不明显。对中和抗体患者血清的进一步表征表明，在大多数情况下，抗体中和了使用不同表达系统（中国仓鼠卵巢细胞和酵母）获得的GM-CSF制剂的生物活性，表明这些抗体可能与内源性产生的GM-CSF发生交叉反应。在使用细胞因子进行治疗前应考虑这些影响，特别是在没有免疫抑制的患者中，因此能够产生有效的免疫应答。我们的研究结果表明，评估细胞因子治疗过程中诱导的中和抗体的产生，可用于预测进一步治疗的临床反应减弱。
In this study, the development of neutralizing and non‐neutralizing GM‐CSF antibodies and the clinical consequences related to the induction of these antibodies were analysed in 20 patients with metastatic colorectal carcinoma receiving a combination therapy of Escherichia coli‐derived GM‐CSF and a colon carcinoma‐reactive MoAb in the absence of any concomitant chemotherapy. The recombinant human GM‐CSF was administered subcutaneously for 10 days every month for 4 months. Following the first cycle of treatment, no GM‐CSF antibodies were detected, but during subsequent therapy, 19 of the 20 patients studied developed GM‐CSF binding antibodies. However, only a proportion (40%) of the 19 antibody‐positive patients developed antibodies that neutralized the biological activity of GM‐CSF in an in vitro bioassay. The presence of GM‐CSF neutralizing antibodies was associated with a significant reduction in GM‐CSF‐induced expansion of leucocytes, neutrophils and eosinophils. Such clinical effects were not apparent in patients with non‐neutralizing antibodies. Further characterization of sera from patients with neutralizing antibodies showed that, in most cases, the antibodies neutralized the biological activity of GM‐CSF preparations derived using different expression systems (chinese hamster ovary cells and yeast), suggesting that these antibodies may have the potential to cross‐react with endogenously produced GM‐CSF. These effects should be considered before therapeutic use of cytokines, particularly in patients who are not immunosuppressed, and therefore capable of mounting an effective immune response. Our results indicate that assessment of production of neutralizing antibodies induced during cytokine therapy can be used to predict diminished clinical response to further therapy.
使用造血生长因子治疗骨髓增生异常综合征。
DOI：
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发表时间：
1990
期刊：
Cancer surveys
影响因子：
--
作者：
Greenberg,PL;Negrin,R;Nagler,A
通讯作者：
Nagler,A