靶向念珠菌细胞壁和细胞表面抗原的单克隆抗体:一项系统评价。
完整摘要 · 中文译文
背景:侵袭性念珠菌病仍与高死亡率相关,而多药耐药菌种如耳念珠菌的出现增加了人们对基于抗体的免疫疗法的兴趣。目的:系统评价靶向念珠菌细胞壁蛋白(CWPs)的单克隆抗体(mAbs)、其保护机制及转化挑战。方法:按照PRISMA 2020指南检索PubMed、Scopus、Web of Science和Embase数据库(2003-2025年)。纳入报告了针对明确CWP靶点且具有保护性数据的特征化单克隆抗体的研究。结果:共12项研究符合纳入标准。确定了10个靶点类别,包括Hwp1、Hyr1、Hsp90、Utr2/Pga31、Ssa1和β-1,2-甘露糖苷/甘露三糖糖表位。保护机制包括调理吞噬作用、生物膜抑制、免疫调节和直接破坏真菌完整性。多种抗体报告了对耳念珠菌的跨物种活性。Mycograb(抗Hsp90)是唯一被确定进入后期(III期)临床评估的被动单克隆抗体;Als3已通过NDV-3A主动疫苗接种平台进入2期评估,而非被动单克隆抗体治疗。结论:念珠菌CWPs是有前景的抗体靶点,但临床转化需要抗体人源化、药代动力学研究以及设计良好的联合试验。
完整摘要 · 英文原文
BACKGROUND: Invasive candidiasis remains associated with high mortality, while multidrug-resistant species such as Candida auris have increased interest in antibody-based immunotherapies. OBJECTIVE: To systematically evaluate monoclonal antibodies (mAbs) targeting Candida cell wall proteins (CWPs), their mechanisms of protection, and translational challenges. METHODS: PubMed, Scopus, Web of Science, and Embase were searched (2003-2025) following PRISMA 2020 guidelines. Studies reporting characterised mAbs against defined CWP targets with protective data were included. RESULTS: Twelve studies met the inclusion criteria. Ten target categories were identified, including Hwp1, Hyr1, Hsp90, Utr2/Pga31, Ssa1, and β-1,2-mannoside/mannotriose glycotopes. Protective mechanisms included opsonophagocytosis, biofilm inhibition, immune modulation, and direct disruption of fungal integrity. Cross-species activity against C. auris was reported for several antibodies. Mycograb (anti-Hsp90) is the only passive mAb identified to have reached advanced (Phase III) clinical evaluation; Als3 has reached Phase 2 evaluation via the NDV-3A active-vaccination platform rather than passive mAb therapy. CONCLUSIONS: Candida CWPs represent promising antibody targets, but clinical translation requires antibody humanisation, pharmacokinetic studies, and well-designed combination trials.