Polymer cancerostatics targeted with an antibody fragment bound via a coiled coil motif: in vivo therapeutic efficacy against murine BCL1 leukemia

0484884 - ÚMCH 2019 RIV DE eng J - Článek v odborném periodiku
Pechar, Michal - Pola, Robert - Janoušková, Olga - Sieglová, Irena - Král, Vlastimil - Fábry, Milan - Tomalová, Barbora - Kovář, Marek
Polymer cancerostatics targeted with an antibody fragment bound via a coiled coil motif: in vivo therapeutic efficacy against murine BCL1 leukemia.
Macromolecular Bioscience. Roč. 18, č. 1 (2018), s. 1-11, č. článku 1700173. ISSN 1616-5187. E-ISSN 1616-5195
Grant CEP: GA MŠMT(CZ) LO1507; GA MŠMT(CZ) LQ1604; GA MZd(CZ) NV16-28594A; GA ČR(CZ) GA16-17207S; GA ČR GA13-12885S
Institucionální podpora: RVO:61389013 ; RVO:68378050 ; RVO:61388971
Klíčová slova: cancer therapy * coiled coil * drug targeting
Obor OECD: Polymer science; Biochemical research methods (UMG-J); Microbiology (MBU-M)
Impakt faktor: 2.895, rok: 2018

A BCL1 leukemia-cell-targeted polymer–drug conjugate with a narrow molecular weight distribution consisting of an N-(2-hydroxypropyl)methacrylamide copolymer carrier and the anticancer drug pirarubicin is prepared by controlled radical copolymerization followed by metal-free click chemistry. A targeting recombinant single chain antibody fragment (scFv) derived from a B1 monoclonal antibody is attached noncovalently to the polymer carrier via a coiled coil interaction between two complementary peptides. Two pairs of coiled coil forming peptides (abbreviated KEK/EKE and KSK/ESE) are used as linkers between the polymer-pirarubicin conjugate and the targeting protein. The targeted polymer conjugate with the coiled coil linker KSK/ESE exhibits 4× better cell binding activity and 2× higher cytotoxicity in vitro compared with the other conjugate. Treatment of mice with established BCL1 leukemia using the scFv-targeted polymer conjugate leads to a markedly prolonged survival time of the experimental animals compared with the treatment using the free drug and the nontargeted polymer-pirarubicin conjugate.
Trvalý link: http://hdl.handle.net/11104/0280967