NY-ESO-1 antigen: A promising frontier in cancer immunotherapy

IF 7.9 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Clinical and Translational Medicine Pub Date : 2024-09-14 DOI:10.1002/ctm2.70020

Alaa Alsalloum, Julia A. Shevchenko, Sergey Sennikov

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Abstract

Significant strides have been made in identifying tumour-associated antigens over the past decade, revealing unique epitopes crucial for targeted cancer therapy. Among these, the New York esophageal squamous cell carcinoma (NY-ESO-1) protein, a cancer/testis antigen, stands out. This protein is presented on the cell surface by major histocompatibility complex class I molecules and exhibits restricted expression in germline cells and various cancers, marking it as an immune-privileged site. Remarkably, NY-ESO-1 serves a dual role as both a tumour-associated antigen and its own adjuvant, implying a potential function as a damage-associated molecular pattern. It elicits strong humoural immune responses, with specific antibody frequencies significantly correlating with disease progression. These characteristics make NY-ESO-1 an appealing candidate for developing effective and specific immunotherapy, particularly for advanced stages of disease. In this review, we provide a comprehensive overview of NY-ESO-1 as an immunogenic tumour antigen. We then explore the diverse strategies for targeting NY-ESO-1, including cancer vaccination with peptides, proteins, DNA, mRNA, bacterial vectors, viral vectors, dendritic cells and artificial adjuvant vector cells, while considering the benefits and drawbacks of each strategy. Additionally, we offer an in-depth analysis of adoptive T-cell therapies, highlighting innovative techniques such as next-generation NY-ESO-1 T-cell products and the integration with lymph node-targeted vaccines to address challenges and enhance therapeutic efficacy. Overall, this comprehensive review sheds light on the evolving landscape of NY-ESO-1 targeting and its potential implications for cancer treatment, opening avenues for future tailored directions in NY-ESO-1-specific immunotherapy.

Highlights

Endogenous immune response: NY-ESO-1 exhibited high immunogenicity, activating endogenous dendritic cells, T cells and B cells.
NY-ESO-1-based cancer vaccines: NY-ESO-1 vaccines using protein/peptide, RNA/DNA, microbial vectors and artificial adjuvant vector cells have shown promise in enhancing immune responses against tumours.
NY-ESO-1-specific T-cell receptor-engineered cells: NY-ESO-1-targeted T cells, along with ongoing innovations in engineered natural killer cells and other cell therapies, have improved the efficacy of immunotherapy.

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NY-ESO-1 抗原：癌症免疫疗法中前景广阔的前沿领域

过去十年来，在鉴定肿瘤相关抗原方面取得了重大进展，揭示了对癌症靶向治疗至关重要的独特表位。其中，纽约食管鳞状细胞癌（NY-ESO-1）蛋白这一癌症/睾丸抗原尤为突出。这种蛋白通过主要组织相容性复合体 I 类分子呈现在细胞表面，在生殖细胞和各种癌症中的表达受到限制，因此是一个免疫优势位点。值得注意的是，NY-ESO-1 具有双重作用，既是肿瘤相关抗原，又是其自身的佐剂，这意味着它可能具有损伤相关分子模式的功能。它能引起强烈的体液免疫反应，特异性抗体频率与疾病进展密切相关。这些特点使 NY-ESO-1 成为开发有效和特异性免疫疗法的理想候选药物，尤其是针对晚期疾病。在本综述中，我们将全面概述作为免疫原的肿瘤抗原 NY-ESO-1。然后，我们探讨了针对 NY-ESO-1 的各种策略，包括使用肽、蛋白质、DNA、mRNA、细菌载体、病毒载体、树突状细胞和人工佐剂载体细胞接种癌症疫苗，同时考虑了每种策略的优点和缺点。此外，我们还深入分析了领养 T 细胞疗法，重点介绍了下一代 NY-ESO-1 T 细胞产品等创新技术以及与淋巴结靶向疫苗的整合，以应对挑战并提高疗效。总之，这篇全面的综述揭示了 NY-ESO-1 靶向不断发展的现状及其对癌症治疗的潜在影响，为 NY-ESO-1 特异性免疫疗法的未来定制方向开辟了道路。亮点内源性免疫反应：NY-ESO-1 具有很高的免疫原性，可激活内源性树突状细胞、T 细胞和 B 细胞。基于 NY-ESO-1 的癌症疫苗：使用蛋白质/肽、RNA/DNA、微生物载体和人工佐剂载体细胞的 NY-ESO-1 疫苗在增强抗肿瘤免疫反应方面表现良好。 NY-ESO-1特异性T细胞受体工程细胞：以 NY-ESO-1 为靶点的 T 细胞，以及工程自然杀伤细胞和其他细胞疗法的不断创新，提高了免疫疗法的疗效。

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来源期刊

Clinical and Translational Medicine Multiple-

CiteScore

15.90

自引率

1.90%

发文量

450

审稿时长

4 weeks

期刊介绍： Clinical and Translational Medicine (CTM) is an international, peer-reviewed, open-access journal dedicated to accelerating the translation of preclinical research into clinical applications and fostering communication between basic and clinical scientists. It highlights the clinical potential and application of various fields including biotechnologies, biomaterials, bioengineering, biomarkers, molecular medicine, omics science, bioinformatics, immunology, molecular imaging, drug discovery, regulation, and health policy. With a focus on the bench-to-bedside approach, CTM prioritizes studies and clinical observations that generate hypotheses relevant to patients and diseases, guiding investigations in cellular and molecular medicine. The journal encourages submissions from clinicians, researchers, policymakers, and industry professionals.