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Toward Anticancer Immunotherapeutics: Well‐Defined Polymer–Antibody Conjugates for Selective Dendritic Cell Targeting
Author(s) -
Tappertzhofen Kristof,
Bednarczyk Monika,
Koynov Kaloian,
Bros Matthias,
Grabbe Stephan,
Zentel Rudolf
Publication year - 2014
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.201400190
Subject(s) - conjugate , chemistry , splenocyte , conjugated system , dendritic cell , population , dispersity , antibody , in vitro , dextran , immune system , biophysics , polymer , biochemistry , immunology , polymer chemistry , biology , organic chemistry , medicine , mathematical analysis , mathematics , environmental health
This paper describes the synthesis of semitelechelic maleimide‐modified N‐ ( 2 ‐hydroxypropyl)methacrylamid) (HPMA) based polymers of narrow dispersity that can be conjugated e.g. to anti‐DEC‐205 antibodies affording “star‐like” topologies (one antibody decorated with several polymer chains). FCS revealed a hydrodynamic diameter of R h = 7.9 nm and SEC narrow dispersity (1.45). Primary in vitro studies with bone marrow derived dendritic cells (DC) show higher cellular binding and uptake rates compared to control samples. Moreover, incubating these conjugates to primary splenocytes demonstrates a much higher affinity to the primary DCs than to any other immune cell population within the spleen. This differentiation is, thereby, much more pronounced for the star‐like conjugates than for conjugates made from polymers statistically modified with anti‐DEC‐205.