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[使用免疫检查点阻断剂治疗黑色素瘤的最新进展]

[Recent Development of Therapies for Melanoma Using Immune Checkpoint Blockades].

作者信息

Okuyama Ryuhei

机构信息

Dept. of Dermatology, Shinshu University School of Medicine.

出版信息

Gan To Kagaku Ryoho. 2016 Jun;43(6):661-5.

Abstract

Melanoma is a highly immune tumor, and tumor-specific T lymphocytes are occasionally induced. Recent progress in tumor immunology has made it possible to clinically develop new medicines targeting immune checkpoint molecules, such as cytotoxic T lymphocyte antigen 4(CTLA-4), programmed cell death 1(PD-1), and programmed cell death 1 ligand 1(PD-L1). CTLA-4 is expressed on naïve T cells and regulatory T cells. Ipilimumab, an anti-CTLA-4 antibody, shows a distinct durable clinical benefit by inhibiting the immunosuppressive function of CTLA-4. PD-1, which is expressed on activated T cells, inhibits T cell responses against tumor cells. The antibodies against PD-1, nivolumab and pembrolizumab, produce anti-tumor responses in melanoma and other cancers due to T cell reactivation. Furthermore, clinical trials of combination therapies using immune checkpoint blockades with molecularly targeted therapies and other chemotherapeutic agents are being conducted. However, immune checkpoint blockades frequently cause immune-related adverse events. Targeted therapies to immune checkpoint molecules are expected to be promising strategies for treatment of melanoma and other cancers.

摘要

黑色素瘤是一种具有高度免疫原性的肿瘤,偶尔会诱导产生肿瘤特异性T淋巴细胞。肿瘤免疫学的最新进展使得临床上能够开发针对免疫检查点分子的新药,如细胞毒性T淋巴细胞相关抗原4(CTLA-4)、程序性细胞死亡蛋白1(PD-1)和程序性细胞死亡蛋白1配体1(PD-L1)。CTLA-4在初始T细胞和调节性T细胞上表达。抗CTLA-4抗体伊匹单抗通过抑制CTLA-4的免疫抑制功能显示出明显持久的临床益处。PD-1在活化的T细胞上表达,抑制T细胞对肿瘤细胞的反应。抗PD-1抗体纳武单抗和派姆单抗由于T细胞的重新激活,在黑色素瘤和其他癌症中产生抗肿瘤反应。此外,正在进行使用免疫检查点阻断剂与分子靶向疗法和其他化疗药物的联合疗法的临床试验。然而,免疫检查点阻断剂经常会引起免疫相关的不良事件。针对免疫检查点分子的靶向疗法有望成为治疗黑色素瘤和其他癌症的有前景的策略。

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