Yifeng Ma, Mary G. Gorman, Juliane Schuphan and Nicole F. Steinmetz
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引用次数: 0
摘要
肿瘤内免疫治疗利用肿瘤微环境来增强局部免疫激活和全身抗肿瘤反应。植物病毒纳米颗粒已经成为这种策略的有效免疫刺激剂。在这里,我们研究聚乙二醇化马铃薯病毒X (PVX-PEG)在b细胞淋巴瘤模型中的作用。我们用双peg n -NHS酯合成了PVX-PEG,并通过SDS-PAGE、动态光散射和透射电镜证实了成功的偶联。聚乙二醇化提高了配方的稳定性,如在生物条件下增加热阻和减少聚集所证明的那样。在体内,PVX- peg表现出长时间的肿瘤滞留,并保持其免疫治疗效果,与天然PVX相当。此外,PVX-PEG的抗体识别显着降低,突出了其临床翻译的潜力。这些结果表明,PVX- peg保留了PVX的免疫刺激益处,同时克服了关键配方和免疫原性挑战,支持其作为一种新型肿瘤内免疫治疗淋巴瘤的进展。
Efficacy of PVX and PEGylated PVX as intratumoral immunotherapy
Intratumoral immunotherapy harnesses the tumor microenvironment to enhance local immune activation and systemic antitumor responses. Plant virus nanoparticles have emerged as potent immunostimulatory agents for this strategy. Here, we investigate the efficacy of PEGylated potato virus X (PVX–PEG) in a B-cell lymphoma model. We synthesized PVX–PEG using bis-PEGn-NHS esters and confirmed successful conjugation through SDS–PAGE, dynamic light scattering, and transmission electron microscopy. PEGylation improved formulation stability, as evidenced by increased thermal resistance and reduced aggregation in biological conditions. In vivo, PVX–PEG exhibited prolonged tumor retention and maintained its immunotherapeutic efficacy, comparable to native PVX. Furthermore, antibody recognition of PVX–PEG was significantly reduced, highlighting its potential for clinical translation. These results suggest that PVX–PEG retains the immunostimulatory benefits of PVX while overcoming key formulation and immunogenicity challenges, supporting its advancement as a novel intratumoral immunotherapy for lymphoma.