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:On the Twentieth Anniversary of Dendritic Cell Vaccines - Riding the Next Wave.
On the Twentieth Anniversary of Dendritic Cell Vaccines - Riding the Next Wave.
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20世纪90年代中期,树突状细胞(DC)生物学和肿瘤抗原识别方面的发现汇聚,促使研究者开始探讨DC作为癌症疫苗佐剂。在Jacques Banchereau及其同事开展的里程碑式临床研究发表20周年之际,我们重新回顾促成第一波DC疫苗临床研究的关键事件,以及我们认为有助于开创如今称作免疫肿瘤学领域的经验教训。必须记住,在免疫检查点疗法和嵌合抗原受体(CAR)T细胞疗法发现之前,人们普遍怀疑免疫疗法的潜在治疗获益。如今回顾,我们可以认识到早期DC癌症疫苗试验帮助研究者持续关注针对恶性细胞的适应性免疫。这些疫苗明确证明可诱导抗原特异性T细胞,而且耐受性良好,尽管客观临床缓解率较低。在约20年后的当前时代,研究显示利用DC疫苗可增加肿瘤特异性T细胞的广度和多样性,并可通过迁移至转移部位促进炎症性肿瘤微环境形成。另见Banchereau等发表于Cancer Res 2001;61:6451–8的相关文章。
In the mid 1990's, a convergence of discoveries in dendritic cell (DC) biology and tumor antigen identification led investigators to study DCs as adjuvants for cancer vaccines. On the twentieth anniversary of a seminal clinical study by Jacques Banchereau and colleagues, we revisit the key events that prompted the initial wave of DC vaccine clinical studies and lessons learned that, in our opinion, helped forge the path for the field that we now call immuno-oncology. It is essential to recall that prior to the discovery of immune checkpoint therapy and chimeric antigen receptor (CAR) T-cell therapy, skepticism prevailed regarding the potential therapeutic benefit of immunotherapies.
In hindsight, we can now appreciate how the early DC cancer vaccine trials helped investigators sustain their attention on adaptive immunity specific for malignant cells. These vaccines demonstrated clear evidence for induction of antigen-specific T cells and were well tolerated despite low rates of objective clinical response.
In the context of the current era some 20 years later, harnessing DC vaccines has been shown to increase the breadth and diversity of tumor-specific T cells, and by trafficking to sites of metastases promote an inflamed tumor microenvironment. See related article by Banchereau and colleagues, Cancer Res 2001; 61:6451-8.
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