Počet záznamů: 1  

Immunogenicity of coiled-coil based drug-free macromolecular therapeutics

  1. 1.
    0442049 - MBU-M 2015 RIV DE eng J - Článek v odborném periodiku
    Kverka, Miloslav - Hartley, J.M. - Chu, T.W. - Yang, J. - Heidchen, R. - Kopeček, J.
    Immunogenicity of coiled-coil based drug-free macromolecular therapeutics.
    Biomaterialien. Roč. 35, č. 2 (2014), s. 5886-5896. ISSN 1616-0177
    Grant CEP: GA MŠk(CZ) EE2.3.30.0003
    Grant ostatní:NIH(US) GM095606
    Institucionální podpora: RVO:61388971
    Klíčová slova: coiled-coil * enantiomers * HPMA copolymer
    Kód oboru RIV: EC - Imunologie

    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.
    Trvalý link: http://hdl.handle.net/11104/0244958