Department of Pharmaceutics, School of Pharmacy, Ningxia Medical University, No.1160 Shengli South Street, Yinchuan, 750004, PR China.
Science and Technology Center, Ningxia Medical University, No.1160 Shengli South Street, Yinchuan, 750004, PR China.
Acta Biomater. 2023 Oct 1;169:489-499. doi: 10.1016/j.actbio.2023.07.059. Epub 2023 Aug 2.
Malignant expansion and rapid metastasis are the main limiting factors to successful treatment of lung cancer. Messenger RNA (mRNA) tumor vaccines are a promising immunotherapeutic treatment for lung cancer as well as other metastatic cancers. Herein, we developed a mPLA/mRNA tumor vaccine (mLPR) to escort mRNA into the cytoplasm and improve immune response with the help of TLR4 agonist mPLA. After nasal administration, the mLPR vaccine stimulated the maturation of dendritic cells, reprogramed M2 macrophages into M1 macrophages, as well cross-activated innate and adaptive immune responses. The mLPR vaccine inhibited the development of lung cancer and reduced bone metastasis by means of immune cell activation, IFN-γ/IL-12 cytokine secretion, and natural killer cell-mediated antibody dependent cellular cytotoxicity. The mPLA/mRNA tumor vaccine will provide ideas and application prospects for the use of mRNA tumor vaccine in the treatment of lung cancer. STATEMENT OF SIGNIFICANCE: Lung cancer and bone metastasis seriously affect patient survival, and traditional treatment methods are inefficient and have many side effects. We have constructed an mRNA vaccine that simultaneously activates the innate immune and adaptive responses of the body, in order to achieve better immunotherapeutic effects. To sum up, we confirmed through vaccine design and in vitro and in vivo immunological studies that the mLPR vaccine stimulated the maturation of dendritic cells, reprogrammed M2 macrophages into M1 macrophages, as well cross activated in vivo and adaptive immune responses.
恶性扩张和快速转移是肺癌成功治疗的主要限制因素。信使 RNA（mRNA）肿瘤疫苗是一种有前途的肺癌免疫治疗方法，也适用于其他转移性癌症。在此，我们开发了一种 mPLA/mRNA 肿瘤疫苗（mLPR），在 TLR4 激动剂 mPLA 的帮助下将 mRNA 导入细胞质，从而提高免疫反应。鼻内给药后，mLPR 疫苗刺激树突状细胞成熟，将 M2 巨噬细胞重编程为 M1 巨噬细胞，并交叉激活先天和适应性免疫反应。mLPR 疫苗通过激活免疫细胞、IFN-γ/IL-12 细胞因子分泌和自然杀伤细胞介导的抗体依赖性细胞毒性抑制肺癌的发展并减少骨转移。mPLA/mRNA 肿瘤疫苗将为 mRNA 肿瘤疫苗在肺癌治疗中的应用提供思路和应用前景。
肺癌和骨转移严重影响患者的生存，传统的治疗方法效率低下且副作用多。我们构建了一种 mRNA 疫苗，同时激活机体的固有免疫和适应性反应，以达到更好的免疫治疗效果。综上所述，我们通过疫苗设计和体外及体内免疫研究证实，mLPR 疫苗刺激树突状细胞成熟，将 M2 巨噬细胞重编程为 M1 巨噬细胞，并交叉激活体内和适应性免疫反应。
