HPMA-based araC co-polymers induced long-term disappearance of engrafted mantle cell lymphomas with no observed toxicity, whereas free araC only led to temporary growth inhibition.
Do HPMA-based araC co-polymers improve anti-lymphoma efficacy compared to free araC in patient-derived MCL xenografts?
HPMA-based cytarabine co-polymers demonstrate superior anti-lymphoma efficacy and safety compared to free cytarabine in preclinical models of mantle cell lymphoma, providing a rationale for clinical translation.
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.
Pola et al. (2020) studied Mantle cell lymphoma (n=6). HPMA-based araC co-polymers vs. Free araC was evaluated on Anti-lymphoma efficacy in vivo. HPMA-based araC co-polymers induced long-term disappearance of engrafted mantle cell lymphomas with no observed toxicity, whereas free araC only led to temporary growth inhibition.