Overcoming resistance to rituximab in relapsed non-Hodgkin lymphomas by antibody-polymer drug conjugates actively targeted by anti-CD38 daratumumab

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389013%3A_____%2F20%3A00531974" target="_blank" >RIV/61389013:_____/20:00531974 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/20:10419799 RIV/61384399:31140/20:00055368 RIV/00064165:_____/20:10419799

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0168365920304831?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0168365920304831?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jconrel.2020.08.042" target="_blank" >10.1016/j.jconrel.2020.08.042</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Overcoming resistance to rituximab in relapsed non-Hodgkin lymphomas by antibody-polymer drug conjugates actively targeted by anti-CD38 daratumumab

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Overcoming resistance to rituximab in relapsed non-Hodgkin lymphomas by antibody-polymer drug conjugates actively targeted by anti-CD38 daratumumab

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10404 - Polymer science

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Controlled Release

ISSN

0168-3659

e-ISSN

—

Svazek periodika

328

Číslo periodika v rámci svazku

10 December

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

11

Strana od-do

160-170

Kód UT WoS článku

000600791600012

EID výsledku v databázi Scopus

2-s2.0-85090112609