Macromolecular Bioscience 2014-10-01

Toward anticancer immunotherapeutics: well-defined polymer-antibody conjugates for selective dendritic cell targeting.

Kristof Tappertzhofen, Monika Bednarczyk, Kaloian Koynov, Matthias Bros, Stephan Grabbe, Rudolf Zentel

Index: Macromol. Biosci. 14(10) , 1444-57, (2014)

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Abstract

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.© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.