Strika Zdeslav, Petković Karlo, Likić Robert
School of Medicine, University of Zagreb, 10000 Zagreb, Croatia.
Division of Clinical Pharmacology and Therapeutics, Department of Internal Medicine, Clinical Hospital Centre Zagreb, 10000 Zagreb, Croatia.
J Pers Med. 2024 Sep 19;14(9):993. doi: 10.3390/jpm14090993.
Glioblastoma (GBM) is the most common and most malignant primary brain tumor, presenting significant treatment challenges due to its heterogeneity, invasiveness, and resistance to conventional therapies. Despite aggressive treatment protocols, the prognosis remains poor, with a median survival time of approximately 15 months. Recent advancements in mRNA vaccine technology, particularly the development of lipid nanoparticles (LNPs), have revitalized interest in mRNA-based therapies. These vaccines offer unique advantages, including rapid production, personalization based on tumor-specific mutations, and a strong induction of both humoral and cellular immune responses. mRNA vaccines have demonstrated potential in preclinical models, showing significant tumor regression and improved survival rates. Early-phase clinical trials have indicated that mRNA vaccines are safe and can induce robust immune responses in GBM patients. Combining mRNA vaccines with other immunotherapeutic approaches, such as checkpoint inhibitors, has shown synergistic effects, further enhancing their efficacy. However, challenges such as optimizing delivery systems and overcoming the immunosuppressive tumor microenvironment remain. Future research should focus on addressing these challenges and exploring combination therapies to maximize therapeutic benefits. Large-scale, randomized clinical trials are essential to validate the efficacy and safety of mRNA vaccines in GBM therapy. The potential to reshape the tumor microenvironment and establish long-term immunological memory underscores the transformative potential of mRNA vaccines in cancer immunotherapy.
胶质母细胞瘤(GBM)是最常见且恶性程度最高的原发性脑肿瘤,因其异质性、侵袭性以及对传统疗法的耐药性而带来了重大的治疗挑战。尽管采用了积极的治疗方案,但其预后仍然很差,中位生存时间约为15个月。mRNA疫苗技术的最新进展,尤其是脂质纳米颗粒(LNP)的开发,重新激发了人们对基于mRNA疗法的兴趣。这些疫苗具有独特的优势,包括生产迅速、基于肿瘤特异性突变进行个性化定制,以及能强烈诱导体液免疫和细胞免疫反应。mRNA疫苗在临床前模型中已显示出潜力,表现出显著的肿瘤消退和生存率提高。早期临床试验表明,mRNA疫苗是安全的,并且可以在GBM患者中诱导强烈的免疫反应。将mRNA疫苗与其他免疫治疗方法(如检查点抑制剂)联合使用已显示出协同效应,进一步提高了它们的疗效。然而,诸如优化递送系统和克服免疫抑制性肿瘤微环境等挑战仍然存在。未来的研究应专注于应对这些挑战并探索联合疗法,以最大化治疗益处。大规模、随机临床试验对于验证mRNA疫苗在GBM治疗中的疗效和安全性至关重要。重塑肿瘤微环境并建立长期免疫记忆的潜力凸显了mRNA疫苗在癌症免疫治疗中的变革潜力。