Overcoming resistance to rituximab in relapsed non-Hodgkin lymphomas by antibody-polymer drug conjugates actively targeted by anti-CD38 daratumumab
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
32860930
DOI
10.1016/j.jconrel.2020.08.042
PII: S0168-3659(20)30483-1
Knihovny.cz E-zdroje
- Klíčová slova
- APDC, Active targeting, CD38, Daratumumab, Drug delivery, Non-Hodgkin lymphoma, Polymer nanomaterials, Rituximab,
- MeSH
- antitumorózní látky * terapeutické užití MeSH
- léčivé přípravky * MeSH
- lidé MeSH
- monoklonální protilátky terapeutické užití MeSH
- nehodgkinský lymfom * farmakoterapie MeSH
- polymery terapeutické užití MeSH
- rituximab MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antitumorózní látky * MeSH
- daratumumab MeSH Prohlížeč
- léčivé přípravky * MeSH
- monoklonální protilátky MeSH
- polymery MeSH
- rituximab MeSH
B-cell non-Hodgkin lymphomas (B-NHL) represent the most common type of hematologic malignancies in the Western hemisphere. The therapy of all B-NHL is based on the combination of different genotoxic cytostatics and anti-CD20 monoclonal antibody (mAb) rituximab. Unfortunately, many patients relapse after the mentioned front-line treatment approaches. The therapy of patients with relapsed/refractory (R/R) B-NHL represents an unmet medical need. We designed, developed and tested novel actively targeted hybrid mAb-polymer-drug conjugate (APDC) containing anti-CD20, anti-CD38 or anti-CD19 mAbs. Biocompatible copolymers based on N-(2-hydroxypropyl)methacrylamide (HPMA) with cytostatic agent doxorubicin attached via stimuli-sensitive hydrazone bond were employed for the mAb grafting. Anti-lymphoma efficacy of the APDC nanotherapeutics was evaluated in vivo on a panel of three patient-derived lymphoma xenografts derived from two patients with R/R B-NHL and one patient with so far untreated B-NHL. In both PDX models derived from patients with R/R B-NHL, the targeting with anti-CD38 antibody daratumumab demonstrated highly improved anti-lymphoma efficacy compared to the targeting with anti-CD20 rituximab, two experimental anti-CD19 antibodies and non-targeted controls. The results represent a proof-of-concept of a new algorithm of personalized anti-tumor therapy based on highly innovative APDC biomaterials.
Citace poskytuje Crossref.org
Targeted Drug Delivery and Theranostic Strategies in Malignant Lymphomas
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