Antibody polymer drug conjugates with increased drug to antibody ratio: CD38-targeting nanomedicines for innovative therapy of relapsed lymphomas
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389013%3A_____%2F25%3A00635781" target="_blank" >RIV/61389013:_____/25:00635781 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11110/25:10499847 RIV/00064165:_____/25:10499847
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S0168365925004961?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0168365925004961?via%3Dihub</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.jconrel.2025.113876" target="_blank" >10.1016/j.jconrel.2025.113876</a>
Alternative languages
Result language
angličtina
Original language name
Antibody polymer drug conjugates with increased drug to antibody ratio: CD38-targeting nanomedicines for innovative therapy of relapsed lymphomas
Original language description
The current frontline therapy for B-cell non-Hodgkin lymphomas (B-NHL), the most frequent hematologic malignancy in the Western hemisphere, is based on immunochemotherapy (ICT), i.e., a combination of genotoxic cytostatics and the anti-CD20 monoclonal antibody (mAb) rituximab. The treatment of relapsed or refractory (R/R) B-NHL remains an unmet medical need. Here, we developed and preclinically characterized a tailored hybrid mAb-polymer-drug conjugate (APDC) composed of the anti-CD38 mAb daratumumab (clinically approved for multiple myeloma therapy) and biocompatible N-(2-hydroxypropyl)methacrylamide (HPMA)-based copolymers conjugated with a cytotoxic payload monomethyl auristatine E (MMAE) via a Val-Cit-para-amino benzyl carbamate spacer cleavable by lysosomal enzymes. This innovative APDC design results in a significantly higher drug-to-antibody ratio (DAR) while maintaining a degree-of-conjugation (DOC) comparable to that of standard antibody-drug conjugates (ADCs). The enhanced anti-lymphoma efficacy of the new APDC nanotherapeutics, compared to standard ADCs, was confirmed in vivo using patient-derived lymphoma xenografts from a patient with R/R B-NHL. These APDC nanomedicines show promise as a personalized targeted chemotherapy approach.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10404 - Polymer science
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Controlled Release
ISSN
0168-3659
e-ISSN
1873-4995
Volume of the periodical
384
Issue of the periodical within the volume
10 August
Country of publishing house
NL - THE KINGDOM OF THE NETHERLANDS
Number of pages
13
Pages from-to
113876
UT code for WoS article
001502323800002
EID of the result in the Scopus database
2-s2.0-105005835433