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首页> 外文期刊>Journal of immunotherapy >Efficacy of an Anti-transferrin Receptor 1 Antibody Against AIDS-related Non-Hodgkin Lymphoma: A Brief Communication
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Efficacy of an Anti-transferrin Receptor 1 Antibody Against AIDS-related Non-Hodgkin Lymphoma: A Brief Communication

机译：抗转铁蛋白受体1抗体抗艾滋病相关的非霍奇金淋巴瘤的功效：简短的交流。

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摘要

The transferrin receptor 1 (TfR1), also known as CD71, is a target for antibody-based cancer immunotherapy due to its high expression on the surface of cancer cells and its ability to internalize. We have previously developed a mouse/human chimeric IgG3 specific for human TfR1 genetically fused to avidin, as a vector to deliver biotinylated anticancer agents into malignant cells. However, we found that this fusion protein (ch128.1Av), and to a lesser extent the same antibody without avidin (ch128.1), exhibits direct cytotoxic activity in vitro against certain malignant hematopoietic cells through the induction of TfR1 degradation and lethal iron starvation. Importantly, both ch128.1 and ch128.1Av have also shown significant anticancer activity in 2 xenograft models of the B-cell malignancy multiple myeloma. It is interesting to note that ch128.1 exhibited superior anticancer activity in both models compared with ch128.1Av, even against malignant cells that show no sensitivity to ch128.1 in vitro. In the present study, we evaluated the efficacy of ch128.1 against an AIDS-related human Burkitt lymphoma cell line (2F7) to determine if ch128.1 can eliminate these cells in vitro and in an in vivo model of AIDS-related non-Hodgkin lymphoma (AIDS-NHL). Even though 2F7 cells expressed high TfR1 levels, these cells lacked sensitivity to the cytotoxicity induced by ch128.1 in vitro. However, ch128.1 showed significant anticancer activity against these AIDS-NHL cells in vivo by significantly prolonging the survival of immunodeficient mice bearing 2F7 tumors. Therefore, ch128.1 warrants further study as a candidate for the treatment of AIDS-NHL and other B-cell malignancies.
机译：转铁蛋白受体1（TfR1）也称为CD71，由于其在癌细胞表面的高表达和内在化能力，因此成为基于抗体的癌症免疫治疗的靶标。我们之前已经开发了一种小鼠/人嵌合IgG3，它对遗传融合至抗生物素蛋白的人TfR1具有特异性，可作为将生物素化抗癌药输送到恶性细胞的载体。但是，我们发现这种融合蛋白（ch128.1Av）和较小程度的不含抗生物素蛋白的相同抗体（ch128.1）通过诱导TfR1降解和致死铁表现出对某些恶性造血细胞的直接细胞毒活性饥饿。重要的是，ch128.1和ch128.1Av在B细胞恶性多发性骨髓瘤的2种异种移植模型中也显示出显着的抗癌活性。有趣的是，与ch128.1Av相比，ch128.1在两个模型中均显示出优异的抗癌活性，甚至针对在体外对ch128.1没有敏感性的恶性细胞。在本研究中，我们评估了ch128.1对与AIDS相关的人类Burkitt淋巴瘤细胞系（2F7）的功效，以确定ch128.1是否可以在体外和在与AIDS相关的非人类淋巴瘤的体内模型中消除这些细胞霍奇金淋巴瘤（AIDS-NHL）。即使2F7细胞表达高TfR1水平，这些细胞对体外ch128.1诱导的细胞毒性缺乏敏感性。但是，ch128.1通过显着延长携带2F7肿瘤的免疫缺陷小鼠的存活期，在体内对这些AIDS-NHL细胞显示出显着的抗癌活性。因此，ch128.1作为治疗AIDS-NHL和其他B细胞恶性肿瘤的候选药物值得进一步研究。

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