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纳米抗体作为创新的免疫检查点调节剂:推动癌症免疫治疗

Nanobodies as innovative immune checkpoint modulators: advancing cancer immunotherapy.

作者信息

Hosseininejad-Chafi Mohammad, Eftekhari Zohre, Oghalaie Akbar, Behdani Mahdi, Sotoudeh Nazli, Kazemi-Lomedasht Fatemeh

机构信息

Venom and Biotherapeutics Molecules Laboratory, Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, 1316943551, Iran.

出版信息

Med Oncol. 2024 Dec 24;42(1):36. doi: 10.1007/s12032-024-02588-y.

DOI:10.1007/s12032-024-02588-y
PMID:39719469
Abstract

The immune system relies on a delicate balance between attacking harmful pathogens and preserving the body's own tissues, a balance maintained by immune checkpoints. These checkpoints play a critical role in preventing autoimmune diseases by restraining excessive immune responses while allowing the immune system to recognize and destroy abnormal cells, such as tumors. In recent years, immune checkpoint inhibitors (ICIs) have become central to cancer therapy, enabling the immune system to target and eliminate cancer cells that evade detection. Traditional antibodies, such as IgGs, have been widely used in immune therapies but are limited by their size and complexity. Nanobodies (Nbs), derived from camelid heavy-chain-only antibodies, offer a promising alternative. These small, stable antibody fragments retain the antigen-binding specificity of traditional antibodies but have enhanced solubility and the ability to target otherwise inaccessible epitopes. This review explores the use of Nbs as ICIs, emphasizing their potential in cancer immunotherapy and other immune-related treatments. Their unique structural properties and small size make Nbs highly effective tools for modulating immune responses, representing a novel approach in the evolving landscape of checkpoint inhibitor therapies.

摘要

免疫系统依赖于攻击有害病原体与保护机体自身组织之间的微妙平衡,这种平衡由免疫检查点维持。这些检查点通过抑制过度免疫反应,同时允许免疫系统识别并摧毁异常细胞(如肿瘤细胞),在预防自身免疫性疾病方面发挥着关键作用。近年来,免疫检查点抑制剂(ICIs)已成为癌症治疗的核心,使免疫系统能够靶向并消除逃避检测的癌细胞。传统抗体,如免疫球蛋白G(IgGs),已广泛应用于免疫治疗,但受其大小和复杂性的限制。源自骆驼科动物仅重链抗体的纳米抗体(Nbs)提供了一种有前景的替代方案。这些小而稳定的抗体片段保留了传统抗体的抗原结合特异性,但具有增强的溶解性以及靶向其他难以接近的表位的能力。本综述探讨了纳米抗体作为免疫检查点抑制剂的应用,强调了它们在癌症免疫治疗和其他免疫相关治疗中的潜力。它们独特的结构特性和小尺寸使纳米抗体成为调节免疫反应的高效工具,代表了不断发展的检查点抑制剂治疗领域中的一种新方法。

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CBL0137 and NKG2A blockade: a novel immuno-oncology combination therapy for Myc-overexpressing triple-negative breast cancers.CBL0137与NKG2A阻断:一种针对Myc过表达三阴性乳腺癌的新型免疫肿瘤联合疗法。
Oncogene. 2025 Apr;44(13):893-908. doi: 10.1038/s41388-024-03259-y. Epub 2024 Dec 21.
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Current Trends and Innovative Approaches in Cancer Immunotherapy.癌症免疫治疗的当前趋势和创新方法。
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Screening, expression and anti-tumor functional identification of anti-LAG-3 nanobodies.
抗 LAG-3 纳米抗体的筛选、表达及抗肿瘤功能鉴定。
Protein Expr Purif. 2024 Oct;222:106522. doi: 10.1016/j.pep.2024.106522. Epub 2024 Jun 6.
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Design and Production of a Novel Anti-PD-1 Nanobody by CDR Grafting and Site-Directed Mutagenesis Approach.通过CDR移植和定点诱变方法设计并生产新型抗PD-1纳米抗体
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Myeloid-derived suppressor cells in cancer: therapeutic targets to overcome tumor immune evasion.癌症中的髓源性抑制细胞:克服肿瘤免疫逃逸的治疗靶点。
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Inhibition of SFTSV replication in humanized mice by a subcutaneously administered anti-PD1 nanobody.皮下注射抗 PD1 纳米抗体抑制人源化小鼠中的 SFTSV 复制。
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T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain as a promising immune checkpoint target for the treatment of SLE.T细胞免疫球蛋白和基于免疫受体酪氨酸的抑制基序结构域作为治疗系统性红斑狼疮的一个有前景的免疫检查点靶点。
Lupus. 2024 Mar;33(3):209-216. doi: 10.1177/09612033241226536. Epub 2024 Jan 30.
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