Individualized Neoantigen-Directed Melanoma Therapy

IF 8.8 1区 医学 Q1 DERMATOLOGY American Journal of Clinical Dermatology Pub Date : 2025-01-29 DOI:10.1007/s40257-025-00920-4
Karam Khaddour, Elizabeth I. Buchbinder
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Abstract

Individualized neoantigen-directed therapy represents a groundbreaking approach in melanoma treatment that leverages the patient’s own immune system to target cancer cells. This innovative strategy involves the identification of unique immunogenic neoantigens (mutated proteins specific to an individual’s tumor) and the development of therapeutic vaccines that either consist of peptide sequences or RNA encoding these neoantigens. The goal of these therapies is to induce neoantigen-specific immune responses, enabling the immune system to recognize and destroy cancer cells presenting the targeted neoantigens. This individualized approach is particularly advantageous given the genetic heterogeneity of melanoma, which exhibits distinct mutations among different patients. In contrast to traditional therapies, neoantigen-directed therapy offers a tailored treatment that potentially reduces off-target side effects and enhances therapeutic efficacy. Recent advances in neoantigen prediction and vaccine development have facilitated clinical trials exploring the combination of neoantigen vaccines with immune checkpoint inhibitors. These trials have shown promising clinical outcomes, underscoring the potential of this personalized approach. This review provides an overview of the rationale behind neoantigen-directed therapies and summarizes the current state of knowledge regarding personalized neoantigen vaccines in melanoma treatment.

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个体化新抗原导向黑色素瘤治疗。
个体化新抗原定向治疗是黑色素瘤治疗的一种突破性方法,它利用患者自身的免疫系统来靶向癌细胞。这一创新策略包括鉴定独特的免疫原性新抗原(针对个体肿瘤的特异性突变蛋白)和开发由肽序列或编码这些新抗原的RNA组成的治疗性疫苗。这些疗法的目标是诱导新抗原特异性免疫反应,使免疫系统能够识别并摧毁呈递靶向新抗原的癌细胞。考虑到黑色素瘤的遗传异质性,这种个体化的方法在不同的患者中表现出不同的突变,尤其有利。与传统疗法相比,新抗原导向疗法提供了一种量身定制的治疗方法,可以潜在地减少脱靶副作用并提高治疗效果。新抗原预测和疫苗开发的最新进展促进了探索新抗原疫苗与免疫检查点抑制剂联合使用的临床试验。这些试验显示出有希望的临床结果,强调了这种个性化方法的潜力。本文综述了新抗原导向疗法背后的基本原理,并总结了黑色素瘤治疗中个性化新抗原疫苗的现状。
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来源期刊
CiteScore
15.20
自引率
2.70%
发文量
84
审稿时长
>12 weeks
期刊介绍: The American Journal of Clinical Dermatology is dedicated to evidence-based therapy and effective patient management in dermatology. It publishes critical review articles and clinically focused original research covering comprehensive aspects of dermatological conditions. The journal enhances visibility and educational value through features like Key Points summaries, plain language summaries, and various digital elements, ensuring accessibility and depth for a diverse readership.
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