Flagellins as Vaccine Adjuvants and Cancer Immunotherapy: Recent Advances and Future Prospects.

IF 4.9 3区 医学 Q2 IMMUNOLOGY
Immunology Pub Date : 2025-06-10 DOI:10.1111/imm.70001
Asma Talukder, Md Mijanur Rahman, Md Sifat Rahi, Dean L Pountney, Ming Q Wei
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引用次数: 0

Abstract

Flagellin, an essential structural protein of bacterial flagella, has emerged as a potent modulator of both specific and nonspecific immunity, demonstrating significant potential as a vaccine adjuvant and carrier. By inducing the release of pro-inflammatory cytokines like IL-1β, TNF-α, IL-6, IL-8, and IL-12, flagellin activates the innate immune system, enhancing antigen-specific adaptive immune responses mediated by tumour-specific type 1 helper T cells and cytotoxic T cells, thus positioning it as a valuable adjuvant or complementary therapy for various cancers and infectious diseases. This review explores recent strategies, innovations, and clinical applications of flagellin-based immunotherapies, particularly in the context of infectious diseases and cancers. Flagellin from Salmonella typhimurium has been extensively studied as a vaccine adjuvant for diseases like HIV, influenza, dengue, West Nile virus, poultry cholera, and bursal diseases and shows promise in treating lung metastasis, melanoma, colon, and prostate cancers. It has also proven effective against multidrug-resistant bacteria, including Pseudomonas aeruginosa and S. typhimurium. Notably, S. typhimurium flagellin-based vaccines for influenza have progressed to clinical trials. Additionally, flagellins from S. typhi, S. enteritidis, P. aeruginosa, and Escherichia coli are being evaluated as vaccine candidates for plague, malaria, and infections caused by P. aeruginosa and E. coli. In cancer therapy, flagellin-based treatments, especially when combined with tumour antigens, have exhibited the ability to enhance anti-tumour immunity and improve patient outcomes. Other flagellin-based vaccines derived from S. Dublin, S. munchen, and Vibrio vulnificus have been employed in the treatment of prostate, lung, liver, breast, cervical, and colorectal cancers, as well as lymphoma, melanoma, and radiation-induced mucositis. Mobilan, a recombinant non-replicating adenovirus vector expressing Salmonella flagellin, is currently in a phase Ib clinical trial for prostate cancer. Overall, bacterial flagellin treatments are generally safe, well-tolerated, and associated with minimal side effects, making them a promising option for managing infectious diseases and cancers.

鞭毛蛋白作为疫苗佐剂和癌症免疫治疗:最新进展和未来展望。
鞭毛蛋白是细菌鞭毛的重要结构蛋白,是特异性和非特异性免疫的有效调节剂,显示出作为疫苗佐剂和载体的巨大潜力。鞭毛蛋白通过诱导IL-1β、TNF-α、IL-6、IL-8和IL-12等促炎细胞因子的释放,激活先天免疫系统,增强由肿瘤特异性1型辅助性T细胞和细胞毒性T细胞介导的抗原特异性适应性免疫反应,从而将其定位为各种癌症和感染性疾病的有价值的辅助或补充治疗。这篇综述探讨了鞭毛蛋白免疫疗法的最新策略、创新和临床应用,特别是在传染病和癌症的背景下。来自鼠伤寒沙门氏菌的鞭毛蛋白已被广泛研究作为艾滋病、流感、登革热、西尼罗河病毒、家禽霍乱和法氏囊疾病等疾病的疫苗佐剂,并在治疗肺转移、黑色素瘤、结肠癌和前列腺癌方面显示出希望。它还被证明对多重耐药细菌有效,包括铜绿假单胞菌和鼠伤寒沙门氏菌。值得注意的是,以鼠伤寒沙门氏菌鞭毛蛋白为基础的流感疫苗已进入临床试验阶段。此外,正在评估伤寒沙门氏菌、肠炎沙门氏菌、铜绿假单胞菌和大肠埃希菌的鞭毛蛋白作为鼠疫、疟疾以及铜绿假单胞菌和大肠埃希菌引起的感染的候选疫苗。在癌症治疗中,以鞭毛蛋白为基础的治疗,特别是与肿瘤抗原联合使用时,已经显示出增强抗肿瘤免疫和改善患者预后的能力。从都柏林沙门氏菌、慕尼黑沙门氏菌和创伤弧菌中提取的其他基于鞭毛蛋白的疫苗已被用于治疗前列腺癌、肺癌、肝癌、乳腺癌、宫颈癌和结直肠癌,以及淋巴瘤、黑色素瘤和辐射引起的粘膜炎。Mobilan是一种表达鞭毛沙门氏菌的重组非复制腺病毒载体,目前正处于前列腺癌的Ib期临床试验中。总的来说,细菌鞭毛蛋白治疗通常是安全的,耐受性良好,副作用最小,使其成为治疗传染病和癌症的有希望的选择。
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来源期刊
Immunology
Immunology 医学-免疫学
CiteScore
11.90
自引率
1.60%
发文量
175
审稿时长
4-8 weeks
期刊介绍: Immunology is one of the longest-established immunology journals and is recognised as one of the leading journals in its field. We have global representation in authors, editors and reviewers. Immunology publishes papers describing original findings in all areas of cellular and molecular immunology. High-quality original articles describing mechanistic insights into fundamental aspects of the immune system are welcome. Topics of interest to the journal include: immune cell development, cancer immunology, systems immunology/omics and informatics, inflammation, immunometabolism, immunology of infection, microbiota and immunity, mucosal immunology, and neuroimmunology. The journal also publishes commissioned review articles on subjects of topical interest to immunologists, and commissions in-depth review series: themed sets of review articles which take a 360° view of select topics at the heart of immunological research.
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