PROTAC 工程化蛋白/DNA 纳米抗原是癌症免疫治疗中树突状细胞疫苗的有效增强剂
PROTAC-Engineered Protein/DNA Nanoantigen is a Potent Booster for Dendritic Cell Vaccines in Cancer Immunotherapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Engineered potent DC vaccine enables closer DC-T cell contact to trigger personalized antitumor immunity.
Engineered potent DC vaccine enables closer DC-T cell contact to trigger personalized antitumor immunity.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
基于患者肿瘤特异性图谱设计的个性化树突状细胞(DC)疫苗在术后辅助癌症治疗中已展现出显著优势。然而,DC激活细胞免疫应答的能力有限,且与T细胞接触不足阻碍了信号转导,导致临床试验中疗效不明确。本研究将纳米级抗原递送与合成免疫学方法相结合,开发了一种制备强效DC疫苗的新策略。该强效DC疫苗可通过MHC I类分子交叉呈递肿瘤抗原激活细胞免疫,并通过表面固定化抗CD3抗体增强DC-T细胞接触以改善激活信号传递。腹股沟区皮下给药后,疫苗有效迁移至淋巴结并展现出优越的抗肿瘤免疫激活能力。值得注意的是,其在小鼠术后肿瘤模型中表现出显著的治疗效果,有效抑制残留肿瘤细胞复发和转移。与PD-1抗体治疗联合使用时,治疗小鼠的生存期进一步延长。总体而言,本研究建立了一个创新的DC疫苗平台,强调了抗原呈递通路和DC-T细胞接触在抗肿瘤免疫中的关键作用,为当前癌症免疫治疗的局限性提供了一种转化解决方案。
Personalized dendritic cell (DC) vaccines designed based on patients' tumor-specific profiles have demonstrated significant advantages in postoperative adjuvant cancer therapy.
However, DC exhibits limited capacity to activate cellular immune responses, and insufficient contact with T cells impede signal transduction, resulting in unclear clinical efficacy in trials.
This study integrated nanoscale antigen delivery with synthetic immunological approaches to develop a novel strategy for preparing potent DC vaccines. The potent DC vaccines could activate cellular immunity by cross-presenting tumor antigens via MHC class I molecules and enhance DC-T cell contact through surface-immobilized anti-CD3 antibodies to improve activation signal transmission. Following subcutaneous administration in the inguinal region, the vaccine effectively migrated to lymph nodes and demonstrated superior antitumor immune activation.
Notably, it exhibited significant therapeutic efficacy in mice postoperative tumor models, effectively inhibiting residual tumor cell recurrence and metastasis. When combined with PD-1 antibody therapy, survival duration was further prolonged in treated mice. Collectively, this study established an innovative DC vaccine platform that highlights the critical roles of antigen presentation pathways and DC-T cell contact in antitumor immunity, offering a translational solution to current limitations in cancer immunotherapy.
MEMBER ACCOUNT
登录成功会直接打开下一页。