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Polymer Cancerostatics Targeted with an Antibody Fragment Bound via a Coiled Coil Motif: In Vivo Therapeutic Efficacy against Murine BCL1 Leukemia

M. Pechar, R. Pola, O. Janoušková, I. Sieglová, V. Král, M. Fábry, B. Tomalová, M. Kovář,

. 2018 ; 18 (1) : . [pub] 20170915

Language English Country Germany

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc19001186

Grant support
NV16-28594A MZ0 CEP Register

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.

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$a Janoušková, Olga $u Institute of Macromolecular Chemistry, Czech Academy of Sciences, Heyrovského nám. 2, 162 06, Prague 6, Czech Republic.
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$a Sieglová, Irena $u Institute of Molecular Genetics, Czech Academy of Sciences, Flemingovo nám. 2, 166 10, Prague 6, Czech Republic.
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$a Král, Vlastimil $u Institute of Molecular Genetics, Czech Academy of Sciences, Flemingovo nám. 2, 166 10, Prague 6, Czech Republic.
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