Pola Robert, Pokorná Eva, Vočková Petra, Böhmová Eliška, Pechar Michal, Karolová Jana, Pankrác Jan, Šefc Luděk, Helman Karel, Trněný Marek, Etrych Tomáš, Klener Pavel
Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovský Sq. 2, 162 06 Prague 6, Czech Republic.
Institute of Pathological Physiology, First Faculty of Medicine, Charles University, Prague, U Nemocnice 5, 128 53 Prague 2, Czech Republic.
Acta Biomater. 2021 Jan 1;119:349-359. doi: 10.1016/j.actbio.2020.11.014. Epub 2020 Nov 11.
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B细胞非霍奇金淋巴瘤（B-NHL）的一种罕见亚型，临床病程呈慢性复发。在诱导和挽救方案中加入阿糖胞苷（araC）已成为大多数MCL患者的标准治疗方法。在本研究中，设计、合成了含有共价结合阿糖胞苷的定制N-（2-羟丙基）甲基丙烯酰胺（HPMA）基聚合物纳米治疗剂（阿糖胞苷共聚物），并使用一组来自新诊断和复发/难治性（R/R）MCL的6个患者来源的淋巴瘤异种移植模型（PDX）在体内评估了它们的抗淋巴瘤疗效。虽然游离阿糖胞苷导致MCL肿瘤生长暂时受到抑制，但阿糖胞苷共聚物诱导移植的淋巴瘤长期消失，即使在来自接受高剂量阿糖胞苷治疗后复发患者的PDX模型中也未观察到毒性。这些结果为在MCL患者的诱导、挽救或姑息治疗中使用基于HPMA的阿糖胞苷共聚物提供了可靠的临床前依据。
