Khaddour Karam, Buchbinder Elizabeth I
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02115, USA.
Melanoma Disease Center, Dana-Farber Cancer Institute, Boston, MA, 02115, USA.
Am J Clin Dermatol. 2025 Mar;26(2):225-235. doi: 10.1007/s40257-025-00920-4. Epub 2025 Jan 29.
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.
个体化新抗原导向疗法是黑色素瘤治疗中的一种开创性方法，它利用患者自身的免疫系统来靶向癌细胞。这种创新策略包括识别独特的免疫原性新抗原（个体肿瘤特有的突变蛋白），以及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现靶向新抗原的癌细胞。鉴于黑色素瘤的基因异质性，即不同患者之间存在不同的突变，这种个体化方法具有特别的优势。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，有可能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推动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。这些试验已显示出有前景的临床结果，凸显了这种个性化方法的潜力。本综述概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当前知识状态。
