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Immunogenicity of coiled-coil based drug-free macromolecular therapeutics
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SYSNO ASEP 0442049 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Immunogenicity of coiled-coil based drug-free macromolecular therapeutics Author(s) Kverka, Miloslav (MBU-M) RID, ORCID
Hartley, J.M. (US)
Chu, T.W. (US)
Yang, J. (US)
Heidchen, R. (US)
Kopeček, J. (US)Number of authors 6 Source Title Biomaterialien - ISSN 1616-0177
Roč. 35, č. 2 (2014), s. 5886-5896Number of pages 10 s. Language eng - English Country DE - Germany Keywords coiled-coil ; enantiomers ; HPMA copolymer Subject RIV EC - Immunology R&D Projects EE2.3.30.0003 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Institutional support MBU-M - RVO:61388971 UT WOS 000336694700025 Annotation A two-component CD20 (non-internalizing) receptor crosslinking system based on the biorecognition of complementary coiled-coil forming peptides was evaluated. Exposure of B cells to Fab'-peptide1 conjugate decorates the cell surface with peptide1; further exposure of the decorated cells to P-(peptide2)(x) (P is the N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer backbone) results in the formation of coiled-coil heterodimers at the cell surface with concomitant induction of apoptosis. The aim of this study was to determine the potential immunogenicity of this therapeutic system that does not contain low molecular weight drugs. Enantiomeric peptides (L- and D-CCE and L- and D-CCK), HPMA copolymer-peptide conjugates, and Fab' fragment-peptide conjugates were synthesized and the immunological properties of peptide conjugates evaluated in vitro on RAW264.7 macrophages and in vivo on immunocompetent BALB/c mice. HPMA copolymer did not induce immune response in vitro and in vivo. Administration of P-peptide conjugates with strong adjuvant resulted in antibody response directed to the peptide. Fab' was responsible for macrophage activation of Fab'-peptide conjugates and a major factor in the antibody induction following i.v. administration of Fab'-conjugates. There was no substantial difference in the ability of conjugates of D-peptides and conjugates of L-peptides to induce Ab response. Workplace Institute of Microbiology Contact Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Year of Publishing 2015
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