Therapeutic mRNA vaccines for lung cancer: reshaping the tumor microenvironment to enhance anti-tumor immunity

Abstract

Traditional treatments for lung cancer include surgery, radiotherapy, chemotherapy, and targeted therapies (such as Erlotinib, Gefitinib, and Crizotinib), as well as immunotherapy (such as Nivolumab and Pembrolizumab). However, these approaches face challenges such as drug resistance, limited efficacy, and significant side effects, making it difficult to improve long-term prognosis. Therefore, tumor vaccines, as a novel immunotherapy strategy, have become a focus of research, aiming to precisely activate anti-tumor immune responses and address the shortcomings of existing treatments. In recent years, mRNA vaccine technology has developed rapidly, especially following the successful application of COVID-19 vaccines, demonstrating its immense potential for rapid development and large-scale production. mRNA cancer vaccines induce durable anti-tumor immune responses and reshape the tumor microenvironment by delivering mRNA encoding tumor-specific antigens, enabling targeted therapy. Through the dual synergistic pathways of direct local modulation by the vector/encoded factors and secondary effects mediated by antigen-specific T-cell activation, the tumor microenvironment is reshaped, thereby inducing durable antitumor immune responses. Against this background, this review systematically evaluates the current status and prospects of mRNA vaccines in lung cancer treatment, with a focus on their progress in precisely modulating the tumor microenvironment, identifying novel tumor antigens, discovering immune biomarkers, and related clinical studies. Additionally, the review discusses the process optimization of lipid nanoparticle (LNP) delivery systems, aiming to provide theoretical support and practical guidance for the development of safe and effective therapeutic vaccine platforms for lung cancer.