Mantle cell lymphoma (MCL) is a rare subtype of B-cell non-Hodgkin lymphoma (B-NHL) with chronically relapsing clinical course. Implementation of cytarabine (araC) into induction and salvage regimen became standard of care for majority of MCL patients. In this study, tailored N-(2-hydroxypropyl)methacrylamide (HPMA)-based polymer nanotherapeutics containing covalently bound araC (araC co-polymers) were designed, synthesized and evaluated for their anti-lymphoma efficacy in vivo using a panel of six patient-derived lymphoma xenografts (PDX) derived from newly diagnosed and relapsed / refractory (R/R) MCL. While free araC led to temporary inhibition of growth of MCL tumors, araC co-polymers induced long-term disappearance of the engrafted lymphomas with no observed toxicity even in the case of PDX models derived from patients, who relapsed after high-dose araC-based treatments. The results provide sound preclinical rationale for the use of HPMA-based araC co-polymers in induction, salvage or palliative therapy of MCL patients.

套细胞淋巴瘤（MCL）是一种B细胞非霍奇金淋巴瘤（B-NHL）罕见的亚型，具有慢性复发性临床病程。阿糖胞苷（araC）在诱导和挽救方案中的应用已成为大多数MCL患者的治疗标准。在这项研究中，设计，合成，评估基于N-（2-羟丙基）甲基丙烯酰胺（HPMA）的共价结合的araC（araC共聚物）的聚合物纳米治疗剂在体内的抗淋巴瘤功效使用一组来自新诊断和复发/难治性（R / R）MCL的六个患者源性淋巴瘤异种移植物（PDX）。尽管游离的araC导致暂时抑制MCL肿瘤的生长，但araC共聚物诱导了移植淋巴瘤的长期消失，即使在源自患者的PDX模型中也未观察到毒性，后者在大剂量araC为基础后复发治疗。该结果为基于HPMA的araC共聚物在MCL患者的诱导，挽救或姑息治疗中的使用提供了合理的临床前理由。