title: Optimization of Folate-Targeted Immunotherapy for the Treatment of Experimental Arthritis.
abstract: Folate-targeted immunotherapy constitutes a powerful method for the treatment of established arthritis in multiple animal models of the disease. The therapy involves immunization of the animal against a hapten to induce anti-hapten antibodies, followed by injection with a folate-hapten conjugate to decorate the surface of folate receptor-positive (activated) macrophages with the antigenic hapten. The hapten-marked macrophages are then recognized by the anti-hapten antibodies and eliminated by immune mechanisms, leading to attenuation of disease symptoms. In the following paper, we optimize the therapy for elimination of inflammatory macrophages and suppression of rheumatoid arthritis symptoms. We also demonstrate a tight correlation between folate receptor-positive macrophage abundance in the liver and inflammation of affected joints. The results suggest that therapies that reduce folate receptor-positive macrophage populations in the body should constitute effective treatments for rheumatoid arthritis.
authors.affiliation: Department of Chemistry, Purdue University, 720 Clinic Drive, West Lafayette, IN, 47907-2084, USA.
authors.forename: Bindu
authors.initials: B
authors.lastname: Varghese
authors.affiliation: Department of Chemistry, Purdue University, 720 Clinic Drive, West Lafayette, IN, 47907-2084, USA.
authors.forename: Chrystal
authors.initials: C
authors.lastname: Paulos
authors.affiliation: Department of Chemistry, Purdue University, 720 Clinic Drive, West Lafayette, IN, 47907-2084, USA. plow@purdue.edu.
authors.forename: Philip S
authors.initials: PS
authors.lastname: Low
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000628:therapy*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000473:pathology; D005492:Folic Acid / Q000276:immunology*; D006241:Haptens / Q000627:therapeutic use; D018796:Immunoconjugates / Q000627:therapeutic use; D007167:Immunotherapy / Q000379:methods*; D008264:Macrophages / Q000187:drug effects*; D058990:Molecular Targeted Therapy / Q000379:methods; D011956:Receptors, Cell Surface / Q000378:metabolism
chemical_list: D006241:Haptens; D018796:Immunoconjugates; D011956:Receptors, Cell Surface; D005492:Folic Acid
keywords: activated macrophage; folate receptor; folate-drug conjugate; immunotherapy; rheumatoid arthritis