• Something wrong with this record ?

Immunogenicity of coiled-coil based drug-free macromolecular therapeutics

M. Kverka, JM. Hartley, TW. Chu, J. Yang, R. Heidchen, J. Kopeček,

. 2014 ; 35 (22) : 5886-96.

Language English Country Netherlands

Document type Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc15008084

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.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc15008084
003      
CZ-PrNML
005      
20150313093704.0
007      
ta
008      
150306s2014 ne f 000 0|eng||
009      
AR
024    7_
$a 10.1016/j.biomaterials.2014.03.063 $2 doi
035    __
$a (PubMed)24767787
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a ne
100    1_
$a Kverka, Miloslav $u Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA; Institute of Microbiology, Academy of Sciences of the Czech Republic, 14220 Prague, Czech Republic.
245    10
$a Immunogenicity of coiled-coil based drug-free macromolecular therapeutics / $c M. Kverka, JM. Hartley, TW. Chu, J. Yang, R. Heidchen, J. Kopeček,
520    9_
$a 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.
650    _2
$a akrylamidy $x aplikace a dávkování $x chemie $x imunologie $7 D000178
650    _2
$a sekvence aminokyselin $7 D000595
650    _2
$a zvířata $7 D000818
650    _2
$a tvorba protilátek $x účinky léků $7 D000917
650    _2
$a buněčné linie $7 D002460
650    _2
$a imunoglobuliny - Fab fragmenty $x aplikace a dávkování $x chemie $x imunologie $7 D007140
650    _2
$a makrofágy $x účinky léků $x imunologie $7 D008264
650    _2
$a myši $7 D051379
650    _2
$a myši inbrední BALB C $7 D008807
650    _2
$a molekulární sekvence - údaje $7 D008969
650    _2
$a peptidy $x aplikace a dávkování $x chemie $x imunologie $7 D010455
650    _2
$a T-lymfocyty $x účinky léků $x imunologie $7 D013601
655    _2
$a časopisecké články $7 D016428
655    _2
$a Research Support, N.I.H., Extramural $7 D052061
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Hartley, Jonathan M $u Department of Bioengineering, University of Utah, Salt Lake City, UT 84112, USA.
700    1_
$a Chu, Te-Wei $u Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA.
700    1_
$a Yang, Jiyuan $u Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA.
700    1_
$a Heidchen, Regina $u Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA.
700    1_
$a Kopeček, Jindřich $u Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA; Department of Bioengineering, University of Utah, Salt Lake City, UT 84112, USA. Electronic address: jindrich.kopecek@utah.edu.
773    0_
$w MED00000753 $t Biomaterials $x 1878-5905 $g Roč. 35, č. 22 (2014), s. 5886-96
856    41
$u https://pubmed.ncbi.nlm.nih.gov/24767787 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20150306 $b ABA008
991    __
$a 20150313093943 $b ABA008
999    __
$a ok $b bmc $g 1065357 $s 890884
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2014 $b 35 $c 22 $d 5886-96 $i 1878-5905 $m Biomaterials $n Biomaterials $x MED00000753
LZP    __
$a Pubmed-20150306

Find record

Citation metrics

Archiving options