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HPMA Copolymer-Bound Doxorubicin Induces Immunogenic Tumor Cell Death
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SYSNO ASEP 0425011 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title HPMA Copolymer-Bound Doxorubicin Induces Immunogenic Tumor Cell Death Author(s) Šírová, Milada (MBU-M) RID, ORCID
Kabešová, Martina (MBU-M) RID
Kovář, Lubomír (MBU-M)
Etrych, Tomáš (UMCH-V) RID, ORCID
Strohalm, Jiří (UMCH-V)
Ulbrich, Karel (UMCH-V) RID
Říhová, Blanka (MBU-M) RIDSource Title Current Medicinal Chemistry. - : Bentham Science Publishers - ISSN 0929-8673
Roč. 20, č. 38 (2013), s. 4815-4826Number of pages 12 s. Language eng - English Country NL - Netherlands Keywords Anti-tumor immune response ; calreticulin ; heat shock proteins Subject RIV CE - Biochemistry R&D Projects GAP301/12/1254 GA ČR - Czech Science Foundation (CSF) Institutional support MBU-M - RVO:61388971 ; UMCH-V - RVO:61389013 UT WOS 000327776700001 Annotation Treatment of murine EL4 T cell lymphoma with N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer conjugates of doxorubicin (Dox) leads to complete tumor regression and to the development of therapy-dependent long-lasting cancer resistance. This phenomenon occurs with two types of Dox conjugates tested, despite differences in the covalent linkage of Dox to the polymer carrier. Such a cancer resistance cannot fully express in conventional treatment with free Dox, due to substantial immunotoxicity of the treatment, which was not observed in the polymer conjugates. In this study, calreticulin (CRT) translocation and high mobility group box-1 protein (HMGB1) release was observed in EL4 cells treated with a conjugate releasing Dox by a pH-dependent manner. As a result, the treated tumor cells were engulfed by dendritic cells (DC) in vitro, and induced their expression of CD80, CD86, and MHC II maturation markers. Conjugates with Dox bound via an amide bond only increased translocation of HSPs to the membrane, which led to an elevated phagocytosis but was not sufficient to induce increase of the maturation markers on DCs in vitro. Both types of conjugates induced engulfment of the target tumor cells in vivo, that was more intense than that seen with free Dox. It means that the induction of anti-tumor immunity documented upon treatment of EL4 lymphoma with HPMA-bound Dox conjugates does not rely solely on CRT-mediated cell death, but involves multiple mechanisms Workplace Institute of Microbiology Contact Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Year of Publishing 2014
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