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, Man₉GlcNAc₂Asn 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，可能会导致新的靶向疗法的发现。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-连接寡糖结构中提供多样性，可作为同源和异源聚糖的独特来源。在植物凝集素衍生的聚糖基序中，Man ₉ GlcNAc ₂Asn 表现出与可能类似于病原体聚糖基序的 CLR 的高亲和力相互作用。因此，当这些聚糖结构域与与选择的纳米载体复合的抗原一起呈递时，可能会使免疫细胞感到困惑并指导抗原交叉呈递——一种由 CD8 ^{+介导的细胞毒性 T 淋巴细胞免疫反应}T细胞。聚糖结构分析引起了相当大的兴趣，因为聚糖被视为比单克隆抗体更好的治疗替代品，因为它们具有成本效益、降低的毒性和副作用以及高特异性。此外，这种方法有助于了解纳米载体表面的多价聚糖是否可以克服低亲和力凝集素-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疗法至关重要。在本次审查中，我们讨论了使用 GlycanBuilder2 对天然凝集素中的聚糖进行结构分析的结果 - 一种基于对天然凝集素的全面文献回顾的软件工具。此外，我们还讨论了多糖配体的方向、配体密度、多个 CLR 的同时靶向和抗原递送纳米载体的设计等多个参数如何影响 CLR 靶向功效。整合这些信息最终将为用于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。