1. Cytarabine nanotherapeutics with increased stability and enhanced lymphoma uptake for tailored highly effective therapy of mantle cell lymphoma.
- Author
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Pola, Robert, Pokorná, Eva, Vočková, Petra, Böhmová, Eliška, Pechar, Michal, Karolová, Jana, Pankrác, Jan, Šefc, Luděk, Helman, Karel, Trněný, Marek, Etrych, Tomáš, and Klener, Pavel
- Subjects
MANTLE cell lymphoma ,CYTARABINE ,LYMPHOMAS ,CELLULAR therapy ,COPOLYMERS ,RITUXIMAB ,DISEASE relapse - Abstract
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. Image, graphical abstract [ABSTRACT FROM AUTHOR]
- Published
- 2021
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