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[黑色素瘤的免疫疗法]

[Immunotherapy of melanomas].

作者信息

Zimmer L, Vaubel J, Schadendorf D

机构信息

Klinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Essen, Hufelandstr. 55, 45133, Essen, Deutschland.

出版信息

Hautarzt. 2012 Dec;63(12):952-8. doi: 10.1007/s00105-012-2470-4.

Abstract

Even early clinical studies showed that adjuvant chemotherapy achieved no therapeutic benefit for melanomas so that in the current guidelines its use is only recommended within the framework of clinical studies. For over 30 years interferons have been used in the adjuvant treatment of primary high risk melanomas as well as in the treatment of metastasized melanomas. They function in an antiviral, immune modulating and antitumor fashion. Direct and indirect effects on tumor cells could be demonstrated for interferons. In Europe low dosage interferon therapy is approved and has become widely established for stage II melanomas, whereas in the USA high dosage therapy for stage III and since March 2011 therapy with pegylated interferon in stage III are also approved. In this article the most important study results will be dealt with in detail. In summary, according to the current study situation therapy with interferon should be offered especially to patients with ulcerated primary melanoma and microscopic lymph node infiltration. Many attempts have been made in the last decades to positively influence the survival time of distant metastasized melanoma by systemic therapy. The recent development of the antibody ipilimumab against cytotoxic T-lymphocyte protein 4 (CTLA-4) could show for the first time a survival advantage in the therapy of melanoma patients in advance stage disease. The licensing of ipilimumab has meant that there is now a new standard available for the second line therapy of malignant melanoma which will be included in the guidelines on therapy of malignant melanoma. A further interesting option for adjuvant therapy is currently vaccination with the recombinant melanoma-associated protein 3 (MAGE-A3) protein in combination with the adjuvant AS015.

摘要

即使早期临床研究表明辅助化疗对黑色素瘤没有治疗益处,因此在当前指南中,仅建议在临床研究框架内使用。30多年来,干扰素一直用于原发性高危黑色素瘤的辅助治疗以及转移性黑色素瘤的治疗。它们具有抗病毒、免疫调节和抗肿瘤作用。已证实干扰素对肿瘤细胞有直接和间接作用。在欧洲,低剂量干扰素疗法已获批准,并已广泛应用于II期黑色素瘤,而在美国,III期高剂量疗法以及自2011年3月起III期聚乙二醇化干扰素疗法也已获批准。本文将详细探讨最重要的研究结果。总之,根据目前的研究情况,干扰素治疗尤其应提供给原发性黑色素瘤溃疡且有微小淋巴结浸润的患者。在过去几十年里,人们进行了许多尝试,通过全身治疗来积极影响远处转移性黑色素瘤的生存时间。抗细胞毒性T淋巴细胞蛋白4(CTLA-4)抗体伊匹单抗的最新研发首次显示出在晚期黑色素瘤患者治疗中的生存优势。伊匹单抗的获批意味着现在有了一种新的标准可用于恶性黑色素瘤的二线治疗,这将被纳入恶性黑色素瘤治疗指南。目前,辅助治疗的另一个有趣选择是用重组黑色素瘤相关蛋白3(MAGE-A3)蛋白联合佐剂AS015进行疫苗接种。

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