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

doi:10.1002/mabi.201400190

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

Macromol Biosci. 2014 Oct;14(10):1444-57. doi: 10.1002/mabi.201400190. Epub 2014 Jun 30.

Authors

Kristof Tappertzhofen¹, Monika Bednarczyk, Kaloian Koynov, Matthias Bros, Stephan Grabbe, Rudolf Zentel

Affiliation

¹ Institute of Organic Chemistry, Johannes Gutenberg-University, Duesbergweg 10-14, 55128, Mainz, Germany.

PMID: 24977785
DOI: 10.1002/mabi.201400190

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.

Keywords: HPMA-polymer; cancer immunotherapy; dendritic cells; polymer-antibody conjugate; tumor vaccine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies / chemistry*
Antibodies / metabolism
Antigens, CD / metabolism
Biological Transport
Cell Survival / drug effects
Dendritic Cells / cytology
Dendritic Cells / drug effects
Dendritic Cells / metabolism*
Drug Carriers / chemistry
Drug Carriers / metabolism*
Drug Carriers / pharmacology
Humans
Immunoconjugates / chemistry
Immunoconjugates / metabolism*
Immunoconjugates / pharmacology
Immunotherapy
Lectins, C-Type / antagonists & inhibitors
Lectins, C-Type / metabolism
Lymphocytes / cytology
Lymphocytes / drug effects
Methacrylates / chemistry*
Mice
Minor Histocompatibility Antigens
Molecular Targeted Therapy
Receptors, Cell Surface / antagonists & inhibitors
Receptors, Cell Surface / metabolism
Spleen / cytology
Spleen / drug effects

Substances

Antibodies
Antigens, CD
DEC-205 receptor
Drug Carriers
Immunoconjugates
Lectins, C-Type
Methacrylates
Minor Histocompatibility Antigens
Receptors, Cell Surface
hydroxypropyl methacrylate