Despite advancements in antibody-based therapies for non-Hodgkin lymphoma (NHL), at least two major therapeutic needs remain unmet: i) heterogenous activation of host immunity towards B cell NHL; and ii) lack of antibody-based therapeutics for T cell NHL. This study explores the molecular characteristics of an adaptable modality called antibody Nanoworms and demonstrates their receptor clustering activity as a means to overcome and address abovementioned needs. To test this, four selected therapeutic receptors of B cell (CD19, CD20, HLA-DR10) and T cell (CD3) NHL were targeted by Nanoworms. Regardless of the target or the cell type, Nanoworms inherently clustered bound receptors on the cell-surface through their multivalency and activated intracellular signaling without any secondary crosslinker. As a sole agent, Nanoworms induced apoptosis by clustering CD20 or HLA-DR10, and arrested the cell cycle upon CD19 clustering. Interestingly, CD3 clustering was particularly advantageous in inducing activation-induced cell death (AICD) in an aggressive form of T cell NHL named Sézary syndrome that is fatal, limited in antibody-based therapeutics, and has poor outcomes to traditional chemotherapy. As Nanoworms can be easily designed to target any receptor for which a scFv is available, they may provide solutions and add therapeutic novelty to underserved diseases.

尽管针对非霍奇金淋巴瘤 (NHL) 的基于抗体的疗法取得了进展，但至少有两个主要的治疗需求仍未得到满足：i) 针对 B 细胞 NHL 的宿主免疫异质激活；ii) 缺乏针对 T 细胞 NHL 的基于抗体的疗法。这项研究探索了一种称为抗体纳米蠕虫的适应性模式的分子特征，并证明了它们的受体聚类活动是克服和满足上述需求的一种手段。为了测试这一点，Nanoworms 靶向了四种选定的 B 细胞（CD19、CD20、HLA-DR10）和 T 细胞（CD3）NHL 治疗受体。无论目标或细胞类型如何，纳米线虫通过其多价性和激活的细胞内信号传导，在细胞表面固有地聚集结合受体，而无需任何二次交联剂。作为独家代理，纳米蠕虫通过聚集 CD20 或 HLA-DR10 诱导细胞凋亡，并在 CD19 聚集时阻止细胞周期。有趣的是，CD3 聚集在诱导活化诱导的细胞死亡 (AICD) 方面特别有利，称为 Sézary 综合征的侵袭性 T 细胞 NHL 形式，这种形式是致命的，在基于抗体的治疗中受到限制，并且与传统化疗相比效果不佳。由于纳米蠕虫可以很容易地设计为针对任何可用的 scFv 受体，它们可以提供解决方案并为服务不足的疾病增加治疗新奇。并且对传统化疗效果不佳。由于纳米蠕虫可以很容易地设计为针对任何可用的 scFv 受体，它们可以提供解决方案并为服务不足的疾病增加治疗新奇。并且对传统化疗效果不佳。由于纳米蠕虫可以很容易地设计为针对任何可用的 scFv 受体，它们可以提供解决方案并为服务不足的疾病增加治疗新奇。