实用医学杂志 ›› 2024, Vol. 40 ›› Issue (10): 1331-1337.doi: 10.3969/j.issn.1006-5725.2024.10.001

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黑色素瘤个体化治疗策略:基于新抗原的特异性免疫治疗

文习之,张晓实()   

  1. 中山大学肿瘤防治中心 (广州 510060 )
  • 收稿日期:2023-10-21 出版日期:2024-05-25 发布日期:2024-05-21
  • 通讯作者: 张晓实 E-mail:zhangxsh@sysucc.org.cn
  • 作者简介:张晓实,博士,教授,主任医师,博士研究生导师。中山大学附属肿瘤医院黑色素瘤单病种首席专家。中国临床肿瘤学会(CSCO)黑色素瘤专家委员会副主任委员、国家癌症中心国家肿瘤质控中心黑色素瘤质控专家委员会副主任委员、广东省临床医学学会肿瘤免疫治疗专委会主任委员、广东省抗癌协会黑色素瘤专委会名誉主任委员等。主持多项国家自然科学基金、广东省自然科学基金。主编出版专著《肿瘤生物治疗学》、《黑色素瘤基础与临床》、《黑色素瘤》和《肿瘤药物治疗方案及综合治疗评价》,发表SCI收录论文50余篇。
  • 基金资助:
    国家自然科学基金项目(82002898)

Immunotherapy based on neoantigen: A personalized treatment strategy for melanoma

Xizhi WEN,Xiaoshi. ZHANG()   

  1. Sun Yat?sen University Cancer Center,Guangzhou 510060,China
  • Received:2023-10-21 Online:2024-05-25 Published:2024-05-21
  • Contact: Xiaoshi. ZHANG E-mail:zhangxsh@sysucc.org.cn

摘要:

免疫检查点抑制剂显著改善黑色素瘤患者预后,但原发及继发性耐药使治疗进入瓶颈期。T细胞受体与肿瘤抗原的结合是免疫治疗发挥作用的关键。肿瘤新抗原(neoantigen)由肿瘤特异性蛋白编码突变产生,在肿瘤细胞中特异表达,在正常组织不表达,不受中枢免疫耐受影响,是免疫治疗的理想靶点。靶向肿瘤新抗原的疫苗、过继性细胞回输及抗体药物等能有效加强和扩大肿瘤特异性免疫反应,促进T细胞识别并清除肿瘤,突破当前治疗瓶颈。本文就黑色素瘤新抗原的个性化治疗现状、最新进展、临床困境及未来发展方向进行讨论分析。

关键词: 黑色素瘤, 新抗原, 免疫治疗

Abstract:

Immune checkpoint inhibitors have significantly improved the prognosis of patients with melanoma, but primary and acquired resistance have led to a bottleneck in treatment. The binding of T-cell receptors to tumor antigens is the key point for immunotherapy. Neoantigens are newly formed antigens generated by tumor cells as a result of various tumor-specific alterations. Neoantigens, identifiable as foreign entities, have the capacity to initiate an immune response unfettered by central and peripheral tolerance mechanisms. This distinctive characteristic renders them highly promising targets in the realm of cancer therapy. Vaccines targeting tumor neoantigens, adoptive cell transfer, and antibody-based therapies can effectively enhance and expand tumor-specific immune responses, promoting T-cell recognition and elimination of tumors, thereby breaking through current treatment bottlenecks. This article discusses the current status, recent advancements, clinical challenges, and future directions in the personalized treatment of melanoma based on neoantigens.

Key words: melanoma, neoantigen, immunotherapy

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