An IgG3-IL-2 fusion protein recognizing a murine B cell lymphoma exhibits effective tumor imaging and antitumor activity.
An IgG3-IL-2 fusion protein recognizing a murine B cell lymphoma exhibits effective tumor imaging and antitumor activity.
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识别小鼠 B 细胞淋巴瘤的 IgG3-IL-2 融合蛋白表现出有效的肿瘤成像和抗肿瘤活性。
DOI：
10.1089/jir.1998.18.597
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Morrison,SL
中科院分区：
文献类型：
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作者：
Penichet,ML;Harvill,ET;Morrison,SL
以抗体(Ab)为基础的肿瘤疗法利用抗体与肿瘤结合的特异性，将Fc功能或相关分子靶向肿瘤部位。我们用一种单抗-白介素2(IL-2)融合蛋白将IL-2传递给小鼠B细胞淋巴瘤(38C13)。这种识别淋巴瘤表面独特型的抗ID IgG3-CH3-IL-2在小鼠中的半衰期大约是IL-2报道的半衰期的17倍。伽马相机研究表明，抗ID IgG3-CH3-IL-2定位于小鼠皮下肿瘤的部位。与单抗和IL-2联合应用相比，抗ID抗体IgG3-CH3-IL-2也显示出更强的抗肿瘤活性。然而，抗肿瘤活性的机制似乎取决于使用的剂量和治疗方案。单剂融合蛋白只在50%的动物中预防了肿瘤，尽管所有幸存者都表现出了一些免疫记忆的证据。尽管多次注射在阻止肿瘤生长方面更有效(87%的幸存者)，但它们在产生保护性免疫记忆方面无效。我们的结果表明，抗体-IL-2融合蛋白将在人类B细胞淋巴瘤和其他相关恶性肿瘤的诊断和治疗中发挥作用。
Antibody (Ab)-based tumor therapeutics use the tumor-binding specificity of the Ab to target Fc functions or associated molecules to the site of the tumor. We have used an Ab-interleukin-2 (IL-2) fusion protein to deliver IL-2 to a murine B cell lymphoma (38C13). This anti-Id IgG3-CH3-IL-2, which recognizes the idiotype present on the surface of the lymphoma has a half-life in mice approximately 17-fold longer than the half-life reported for IL-2. Gamma camera studies showed that anti-Id IgG3-CH3-IL-2 localizes at the site of a subcutaneous tumor in mice. The anti-Id IgG3-CH3-IL-2 also shows enhanced antitumor activity compared with the combination of Ab and IL-2 administered together. However, the mechanism of antitumor activity appears to depend on the dose and the treatment schedule used. A single dose of fusion protein prevented tumor in only 50% of the animals, although all the survivors showed some evidence of immunologic memory. Although multiple doses are more effective in preventing tumor growth (87% survivors), they are ineffective in generating protective immunologic memory. Our results suggest that Ab-IL-2 fusion proteins will be useful in the diagnosis and treatment of human B cell lymphomas and other related malignancies.