title: Toward anticancer immunotherapeutics: well-defined polymer-antibody conjugates for selective dendritic cell targeting.
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.
authors: Institute of Organic Chemistry, Johannes Gutenberg-University, Duesbergweg 10-14, 55128, Mainz, Germany.
authors: Kristof
authors: K
authors: Tappertzhofen
authors: Monika
authors: M
authors: Bednarczyk
authors: Kaloian
authors: K
authors: Koynov
authors: Matthias
authors: M
authors: Bros
authors: Stephan
authors: S
authors: Grabbe
authors: Rudolf
authors: R
authors: Zentel
mesh_terms: D000818:Animals; D000906:Antibodies / Q000737:chemistry* / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D001692:Biological Transport; D002470:Cell Survival / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D007167:Immunotherapy; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D008689:Methacrylates / Q000737:chemistry*; D051379:Mice; D015778:Minor Histocompatibility Antigens; D058990:Molecular Targeted Therapy; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000187:drug effects
chemical_list: D000906:Antibodies; D015703:Antigens, CD; C093569:DEC-205 receptor; D004337:Drug Carriers; D018796:Immunoconjugates; D037181:Lectins, C-Type; D008689:Methacrylates; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface; C032802:hydroxypropyl methacrylate
keywords: HPMA-polymer; cancer immunotherapy; dendritic cells; polymer-antibody conjugate; tumor vaccine