Interferons can upregulate the expression of the tumor associated antigen G250-MN/CA IX, a potential target for (radio)immunotherapy of renal cell carcinoma
Interferons can upregulate the expression of the tumor associated antigen G250-MN/CA IX, a potential target for (radio)immunotherapy of renal cell carcinoma
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DOI：
10.1089/108497803322287619
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发表时间：
2003-08-01
影响因子：
3.4
通讯作者：
Boerman, OC
中科院分区：
文献类型：
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作者：
Brouwers, AH;Frielink, C;Boerman, OC
背景：白细胞介素-2 (IL-2) 和干扰素-α (IFN-α) 可以在少数 (5-25%) 转移性肾细胞癌 (RCC) 患者中诱导治疗反应。 G250-MN/CA IX 是一种在大多数透明细胞 RCC 上表达的肿瘤相关抗原，是基于 G250 抗体的（放射）免疫治疗的潜在（放射）免疫治疗靶点。我们研究了生物反应调节剂 (BRM) IL-2、IFN-α 和 IFN-gamma 对 RCC 细胞上 G250 抗原表达的影响。方法：在体外，在不同浓度的 BRM 存在下培养 RCC 细胞后，通过流式细胞术 (FCM) 测量 G250 抗原的表达。此外，通过 Scatchard 分析定量测定每个细胞的 G250 表位数量。结果：在存在 IFN-α 或 IFN-γ 的条件下培养的 RCC 细胞中观察到 G250 表达上调，而添加 IL-2 则没有影响。对于两种 IFN，观察到 G250 抗原表达和 IFN 剂量之间存在明显的剂量反应关系，其中 IFN-γ 是更有效的药物。 G250 表达可上调四倍。有趣的是，IFN-α 和 IFN-γ 组合的效果显示，与单独使用任何一种 IFN 相比，G250 表达的上调更为明显。结论：根据体外实验，IFN-α和IFN-γ可以上调G250的表达。体内研究有必要调查是否由于 IFN 治疗而导致 G250 表达增加，以及 G250 表达增加是否可以增强基于 G250 抗体的（放射）免疫疗法的治疗效果。
Background: Interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) can induce therapeutic responses in a minority (5-25%) of patients with metastatic renal cell carcinoma (RCC). G250-MN/CA IX, a tumor-associated antigen expressed on the majority of clear cell RCCs, is a potential (radio)immunotherapeutic target for G250-antibody based (radio)immunotherapy. We investigated the effect of the biological response modifiers (BRMs) IL-2, IFN-alpha, and IFN-gamma on the expression of the G250 antigen on RCC cells. Methods: In vitro, the expression of the G250 antigen was measured by flow cytometry (FCM) after culturing RCC cells in the presence of various concentrations of the BRMs. Additionally, the number of G250 epitopes per cell was determined quantitatively by Scatchard analysis. Results: Upregulation of G250 expression was observed on RCC cells cultured in the presence of IFN-alpha or IFN-gamma, whereas the addition of IL-2 had no effect. For both IFNs a clear dose-response relation between G250 antigen expression and IFN dose was observed, with IFN-gamma being the more potent agent. G250 expression could be upregulated four-fold. Interestingly, the effect of combining IFN-alpha and IFN-gamma revealed a more pronounced upregulation of G250 expression than either one of the IFNs alone. Conclusions: On the basis of in vitro experiments, G250 expression can be upregulated by IFN-alpha and IFN-gamma. In vivo studies are warranted to investigate whether due to IFN treatment increased G250 expression occurs, and whether increased G250 expression can enhance the therapeutic efficacy of G250-antibody based (radio)immunotherapy.