Gupta Bhavika, Sadaria Daizy, Warrier Vaishnavi U, Kirtonia Anuradha, Kant Ravi, Awasthi Amit, Baligar Prakash, Pal Jayanta K, Yuba Eiji, Sethi Gautam, Garg Manoj, Gupta Rajesh Kumar
Protein Biochemistry Research Laboratory, Dr. D. Y. Patil Biotechnology & Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth (Deemed to be University), Tathawade, Pune, 411033, Maharashtra, India.
Amity Institute of Molecular Medicine and Stem Cell Research (AIMMSCR), Amity University Uttar Pradesh, Noida, 201313, India.
Semin Cancer Biol. 2022 May;80:87-106. doi: 10.1016/j.semcancer.2020.02.005. Epub 2020 Feb 14.
Plant lectins, a natural source of glycans with a therapeutic potential may lead to the discovery of new targeted therapies. Glycans extracted from plant lectins are known to act as ligands for C-type lectin receptors (CLRs) that are primarily present on immune cells. Plant-derived glycosylated lectins offer diversity in their N-linked oligosaccharide structures that can serve as a unique source of homogenous and heterogenous glycans. Among the plant lectins-derived glycan motifs, ManGlcNAcAsn exhibits high-affinity interactions with CLRs that may resemble glycan motifs of pathogens. Thus, such glycan domains when presented along with antigens complexed with a nanocarrier of choice may bewilder the immune cells and direct antigen cross-presentation - a cytotoxic T lymphocyte immune response mediated by CD8 T cells. Glycan structure analysis has attracted considerable interest as glycans are looked upon as better therapeutic alternatives than monoclonal antibodies due to their cost-effectiveness, reduced toxicity and side effects, and high specificity. Furthermore, this approach will be useful to understand whether the multivalent glycan presentation on the surface of nanocarriers can overcome the low-affinity lectin-ligand interaction and thereby modulation of CLR-dependent immune response. Besides this, understanding how the heterogeneity of glycan structure impacts the antigen cross-presentation is pivotal to develop alternative targeted therapies. In the present review, we discuss the findings on structural analysis of glycans from natural lectins performed using GlycanBuilder2 - a software tool based on a thorough literature review of natural lectins. Additionally, we discuss how multiple parameters like the orientation of glycan ligands, ligand density, simultaneous targeting of multiple CLRs and design of antigen delivery nanocarriers may influence the CLR targeting efficacy. Integrating this information will eventually set the ground for new generation immunotherapeutic vaccine design for the treatment of various human malignancies.
植物凝集素是一种具有治疗潜力的天然聚糖来源，可能会促成新的靶向治疗方法的发现。已知从植物凝集素中提取的聚糖可作为主要存在于免疫细胞上的C型凝集素受体（CLR）的配体。植物来源的糖基化凝集素在其N-连接寡糖结构上具有多样性，可作为同质和异质聚糖的独特来源。在植物凝集素衍生的聚糖基序中，甘露糖-葡萄糖胺-天冬酰胺与CLR表现出高亲和力相互作用，这可能类似于病原体的聚糖基序。因此，当这种聚糖结构域与与所选纳米载体复合的抗原一起呈现时，可能会迷惑免疫细胞并直接引导抗原交叉呈递——一种由CD8 T细胞介导的细胞毒性T淋巴细胞免疫反应。由于聚糖具有成本效益、毒性和副作用较低以及特异性高等优点，相比单克隆抗体，聚糖被视为更好的治疗选择，因此聚糖结构分析引起了相当大的兴趣。此外，这种方法将有助于了解纳米载体表面的多价聚糖呈现是否能够克服低亲和力的凝集素-配体相互作用，从而调节CLR依赖性免疫反应。除此之外，了解聚糖结构的异质性如何影响抗原交叉呈递对于开发替代靶向治疗方法至关重要。在本综述中，我们讨论了使用GlycanBuilder2对天然凝集素的聚糖进行结构分析的结果，GlycanBuilder2是一种基于对天然凝集素的全面文献综述的软件工具。此外，我们还讨论了聚糖配体的方向、配体密度、同时靶向多个CLR以及抗原递送纳米载体的设计等多个参数如何影响CLR靶向效果。整合这些信息最终将为治疗各种人类恶性肿瘤的新一代免疫治疗疫苗设计奠定基础。
