决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Recent advancements in lipid-mRNA nanoparticles as a treatment option for cancer immunotherapy.
mRNA 在开发具有多种医学应用的治疗性药物和疫苗方面优于其他生物分子,目前研究人员正在各个生物医学领域探索这些应用。基于脂质的 mRNA 纳米颗粒可以通过增强 mRNA 的稳定性、促进其细胞摄取以及促进其内体逃逸来提高 mRNA 的效力。通过将其表面与所需的配体或靶向剂缀合,可以提高这些治疗剂的靶向性。脂质-mRNA 纳米颗粒正越来越多地被纳入癌症免疫治疗应用,包括疫苗、单克隆抗体和CAR-T 细胞治疗,并且几种此类纳米颗粒正在临床试验中进行评估。进一步研究评估脂质-mRNA 纳米颗粒转染效率的关键变量将加速改进治疗剂的开发。
癌症仍然是全球严重的健康问题,针对其治疗正在开发不同的方法。近年来,利用免疫系统作为治疗癌症的策略势头渐增。过去几十年中,信使RNA(mRNA)已被评估为开发先进癌症免疫疗法的新兴资源。然而,在细胞外区室中的降解以及在内体逃逸过程中的降解仍然是高效mRNA递送的障碍,并限制了该方法的治疗应用。涵盖领域:基于脂质的纳米载体作为非病毒mRNA载体正受到显著关注。已开发出多种基于脂质的纳米载体类型,以增强mRNA分子的稳定性,促进其转染,并确保递送至适合进一步加工的细胞内区室。本综述讨论了利用脂质开发新型mRNA递送系统以实现有效癌症免疫治疗。
BACKGROUND: Cancer remains a serious health concern worldwide, and different approaches are being developed for its treatment. The strategy to use the immune system as an approach for treating cancer has recently gained momentum. Messenger RNA (mRNA) has been assessed as an up-and-coming resource for the evolution of advanced cancer immunotherapies over the past decades. However, degradation in extracellular compartments and during endosomal escape remain obstacles for efficient mRNA delivery and limit the therapeutic applications of this approach. AREA COVERED: Lipid-based nanocarriers are gaining significant attention as non-viral mRNA vectors. Various lipid-based nanocarrier types have been developed to enhance the stability of mRNA molecules, facilitate their transfection, and ensure delivery to an intracellular compartment suitable for further processing. This review discusses the development of novel mRNA delivery systems using lipids for effective cancer immunotherapy. EXPERT OPINION: mRNAs are superior to other biomolecules for developing therapeutic drugs and vaccines with multiple medical applications that are currently being explored by researchers in various biomedical fields. Lipid-based mRNA nanoparticles can improve the potency of the mRNA by enhancing its stability, enabling its cellular uptake, and facilitating its endosomal escape. Targetability of these therapeutics can be increased by conjugating their surface with the desired ligands or targeting agents. Lipid-mRNA nanoparticles are increasingly being incorporated in cancer immunotherapy applications, including vaccines, monoclonal antibodies, and chimeric antigen receptor T-cell treatment, and several such nanoparticles are being assessed in clinical trials. Further research that assesses key variables for transfection efficiency of lipid-mRNA nanoparticles will expedite the development of improved therapeutics.
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