Novel IL-2-Poly(HPMA)Nanoconjugate Based Immunotherapy

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389013%3A_____%2F15%3A00448356" target="_blank" >RIV/61389013:_____/15:00448356 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61388971:_____/15:00448356

Výsledek na webu

<a href="http://dx.doi.org/10.1166/jbn.2015.2114" target="_blank" >http://dx.doi.org/10.1166/jbn.2015.2114</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1166/jbn.2015.2114" target="_blank" >10.1166/jbn.2015.2114</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Novel IL-2-Poly(HPMA)Nanoconjugate Based Immunotherapy

Popis výsledku v původním jazyce

Interleukin-2 (IL-2) possesses a strong stimulatory activity for activated T and NK cells and it is an attractive molecule for immunotherapy. Nevertheless, extremely short half-life and severe toxicities associated with high-dose IL-2 treatment are serious and limiting drawbacks. In order to increase IL-2 half-life in vivo, we covalently conjugated synthetic semitelechelic polymeric carrier based on N-(2-hydroxypropyl)methacrylamide (HPMA) to IL-2. Thus, we synthesized IL-2-poly(HPMA) conjugate containing 2-3 polymer chains per IL-2 molecule in average. Such conjugate has lower biologic activity in comparison to IL-2 in vitro. However, it exerts much higher activity than IL-2 in vivo as shown by expansion of memory CD8(+) T, NK, NKT, gamma delta T and Treg cells. Moreover, IL-2-poly(HPMA) extremely effectively potentiates CD8(+) T cell peptide-based vaccination. IL-2-poly(HPMA) shows also much longer half-time in circulation than IL-2 (similar to 4 h versus similar to 5 min). Collectively, modification of IL-2 with poly(HPMA) chains dramatically improves its potency and pharmacologic features in vivo, which have implications for immunotherapy. To our knowledge, this is the first proof-of-concept report of the use of polymer/protein modification of IL-2 to obtain more pronounced biological activity

Název v anglickém jazyce

Novel IL-2-Poly(HPMA)Nanoconjugate Based Immunotherapy

Popis výsledku anglicky

Interleukin-2 (IL-2) possesses a strong stimulatory activity for activated T and NK cells and it is an attractive molecule for immunotherapy. Nevertheless, extremely short half-life and severe toxicities associated with high-dose IL-2 treatment are serious and limiting drawbacks. In order to increase IL-2 half-life in vivo, we covalently conjugated synthetic semitelechelic polymeric carrier based on N-(2-hydroxypropyl)methacrylamide (HPMA) to IL-2. Thus, we synthesized IL-2-poly(HPMA) conjugate containing 2-3 polymer chains per IL-2 molecule in average. Such conjugate has lower biologic activity in comparison to IL-2 in vitro. However, it exerts much higher activity than IL-2 in vivo as shown by expansion of memory CD8(+) T, NK, NKT, gamma delta T and Treg cells. Moreover, IL-2-poly(HPMA) extremely effectively potentiates CD8(+) T cell peptide-based vaccination. IL-2-poly(HPMA) shows also much longer half-time in circulation than IL-2 (similar to 4 h versus similar to 5 min). Collectively, modification of IL-2 with poly(HPMA) chains dramatically improves its potency and pharmacologic features in vivo, which have implications for immunotherapy. To our knowledge, this is the first proof-of-concept report of the use of polymer/protein modification of IL-2 to obtain more pronounced biological activity

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

EC - Imunologie

OECD FORD obor

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Projekt

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

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2015

Kód důvěrnosti údajů

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

Název periodika

Journal of Biomedical Nanotechnology

ISSN

1550-7033

e-ISSN

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Svazek periodika

11

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

1662-1673

Kód UT WoS článku

000359391700013

EID výsledku v databázi Scopus

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