Kabut Jacek, Stępień Grzegorz J, Furgoł Tomasz, Miciak Michał, Nafalska Natalia, Stopyra Małgorzata, Jezierzański Marcin, Feret Krzysztof, Gisterek-Grocholska Iwona
Department of Oncology and Radiotherapy, Silesian Medical University, 40-514 Katowice, Poland.
Faculty of Medicine, Medical University of Lodz, 90-419 Lodz, Poland.
Biomedicines. 2025 Sep 7;13(9):2187. doi: 10.3390/biomedicines13092187.
Malignant neoplasms, like non-small cell lung cancer (NSCLC), remain a major global health challenge. Lung cancer is the leading cause of cancer-related deaths worldwide, with over two million new cases and 1.8 million deaths annually. NSCLC accounts for approximately 85% of cases, underscoring its substantial public health impact. Advances in molecular biology have driven the development of new therapies beyond traditional treatments. Among them, mRNA-based immunoadjuvant therapies, like cancer vaccines, have emerged as promising utilities in NSCLC by triggering targeted immune responses. The aim of this paper is to review ongoing and completed studies on mRNA vaccines in NSCLC. The efficacy of mRNA vaccines in NSCLC relies on the identification of immunogenic tumor-specific antigens, frequently derived from genomic profiling databases. Completed clinical trials have assessed the safety and potential benefit of selected mRNA vaccines-such as CV9202-administered alone or in combination with radiotherapy or tyrosine kinase inhibitors. Ongoing studies are exploring the therapeutic potential of mRNA-based approaches targeting defined molecular alterations in NSCLC, particularly in conjunction with Programmed Death-Ligand 1 (PD-L1) immune checkpoint inhibitors to enhance antitumor immune responses. mRNA vaccines have emerged as a promising therapeutic option for NSCLC, with the potential to enhance immune responses and limit tumor progression, as demonstrated in ongoing clinical trials. They offer the possibility of personalized treatment with relatively few side effects. However, larger and long-term studies are required to fully confirm their safety and efficacy. Future research should aim to identify the most effective antigens, enhance stability, and refine delivery strategies to improve efficacy and personalization, while also addressing immune suppression within the tumor microenvironment.
恶性肿瘤，如非小细胞肺癌（NSCLC），仍然是全球主要的健康挑战。肺癌是全球癌症相关死亡的主要原因，每年有超过两百万新发病例和180万例死亡。NSCLC约占病例的85%，凸显了其对公共卫生的重大影响。分子生物学的进展推动了超越传统治疗方法的新疗法的发展。其中，基于mRNA的免疫佐剂疗法，如癌症疫苗，通过触发靶向免疫反应，已成为NSCLC中有前景的治疗手段。本文旨在综述NSCLC中正在进行和已完成的mRNA疫苗研究。NSCLC中mRNA疫苗的疗效依赖于免疫原性肿瘤特异性抗原的鉴定，这些抗原通常来自基因组分析数据库。已完成的临床试验评估了所选mRNA疫苗（如单独使用或与放疗或酪氨酸激酶抑制剂联合使用的CV9202）的安全性和潜在益处。正在进行的研究正在探索基于mRNA的方法针对NSCLC中特定分子改变的治疗潜力，特别是与程序性死亡配体1（PD-L1）免疫检查点抑制剂联合使用以增强抗肿瘤免疫反应。正如正在进行的临床试验所表明的，mRNA疫苗已成为NSCLC有前景的治疗选择，有可能增强免疫反应并限制肿瘤进展。它们提供了副作用相对较少的个性化治疗的可能性。然而，需要更大规模和长期的研究来充分证实其安全性和疗效。未来的研究应旨在确定最有效的抗原，提高稳定性，并优化递送策略以提高疗效和个性化，同时还要解决肿瘤微环境中的免疫抑制问题。
