title: Effectiveness of slow-release systems in CD40 agonistic antibody immunotherapy of cancer.
abstract: Slow-release delivery has great potential for specifically targeting immune-modulating agents into the tumor-draining area. In prior work we showed that local treatment of slowly delivered anti-CD40 antibody induced robust anti-tumor CD8+ T cell responses without systemic toxicity. We now report on the comparison of two slow-release delivery systems for their use in antibody-based immunotherapy of cancer. Anti-CD40 agonistic antibody delivered locally in mineral oil Montanide ISA 51 or in dextran-based microparticles activated tumor-specific T cell activation. Both slow-release formulations significantly decreased systemic side-effects compared to systemic administration of anti-CD40 antibody. However, dextran-based microparticles caused serious local inflammation associated with unwanted rapid outgrowth of tumors instead of the tumor clearance observed with delivery in Montanide. We therefore conclude that Montanide ISA 51 is to be preferred as a slow-release agent for CD40 agonist immunotherapy of cancer.
authors: Department of Immunohematology and Bloodtransfusion, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: M.F.Herbert-Fransen@lumc.nl.
authors: Marieke F
authors: MF
authors: Fransen
authors: Department of Immunohematology and Bloodtransfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors: Robert A
authors: RA
authors: Cordfunke
authors: Department of Immunohematology and Bloodtransfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors: Marjolein
authors: M
authors: Sluijter
authors: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, Utrecht, The Netherlands.
authors: Mies J
authors: MJ
authors: van Steenbergen
authors: Department of Immunohematology and Bloodtransfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors: Jan W
authors: JW
authors: Drijfhout
authors: Department of Immunohematology and Bloodtransfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors: Ferry
authors: F
authors: Ossendorp
authors: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, Utrecht, The Netherlands.
authors: Wim E
authors: WE
authors: Hennink
authors: Department of Immunohematology and Bloodtransfusion, Leiden University Medical Center, Leiden, The Netherlands; ISA Pharmaceuticals, Leiden, The Netherlands.
authors: Cornelis J M
authors: CJ
authors: Melief
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019013:CD40 Antigens / Q000819:agonists* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics / Q000627:therapeutic use; D003911:Dextrans / Q000493:pharmacokinetics*; D006825:Hybridomas / Q000276:immunology; D007167:Immunotherapy; D008297:Male; D008353:Mannitol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000628:therapy*; D009829:Oleic Acids / Q000493:pharmacokinetics*
chemical_list: D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D003692:Delayed-Action Preparations; D003911:Dextrans; D009829:Oleic Acids; C477385:montanide ISA 51; D008353:Mannitol
keywords: Cancer immunotherapy; Microparticles; Monoclonal antibodies; Side-effects; Slow-release