Nejvíce citovaný článek - PubMed ID 19047168
Overcoming immunoescape mechanisms of BCL1 leukemia and induction of CD8+ T-cell-mediated BCL1-specific resistance in mice cured by targeted polymer-bound doxorubicin
PURPOSE: In vivo efficacy and safety of HPMA-based copolymers armed with doxorubicin via a spacer containing pH-sensitive linkage that can be prepared within a broad range of attached drug contents (1) was tested in murine tumor models. METHODS: Mice bearing T cell lymphoma EL4 or B cell lymphoma 38C13 were treated with a single dose of the conjugate (15, 25, and 75 mg Dox eq./kg i.v.) in a therapeutic regime. Anti-tumor resistance of the cured animals was proved by a second challenge with a lethal dose of tumor cells without additional treatment. RESULTS: The content of drug bound to the polymer is an important parameter in relation to the conjugate therapeutic efficacy. The best anti-tumor effects were produced by conjugates with 10 - 13 wt% of bound doxorubicin. Free doxorubicin up to 4.6% relative to total drug content had no impact on the treatment efficacy and acute toxicity. The conjugates induced a complete cure of mice and regular treatment-dependent development of specific anti-tumor resistance. No myelosuppression or organ damage was observed. CONCLUSIONS: A well-defined HPMA copolymer-doxorubicin conjugate with pH-sensitive drug release is a good candidate for clinical trials as it has remarkable anti-tumor efficacy and a favorable safety profile.
- MeSH
- doxorubicin analogy a deriváty chemická syntéza farmakokinetika farmakologie MeSH
- imunomodulace účinky léků MeSH
- koncentrace vodíkových iontů MeSH
- kyseliny polymethakrylové chemická syntéza farmakokinetika farmakologie MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nosiče léků chemická syntéza farmakokinetika farmakologie MeSH
- polymery * chemická syntéza farmakokinetika farmakologie MeSH
- proliferace buněk účinky léků MeSH
- protinádorová antibiotika farmakokinetika farmakologie MeSH
- xenogenní modely - testy protinádorové aktivity MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- doxorubicin-N-(2-hydroxypropyl)methacrylamide copolymer conjugate MeSH Prohlížeč
- doxorubicin MeSH
- kyseliny polymethakrylové MeSH
- nosiče léků MeSH
- polymery * MeSH
- protinádorová antibiotika MeSH
