title: Targeted Delivery of Immunomodulators to Lymph Nodes.
abstract: Active-targeted delivery to lymph nodes represents a major advance toward more effective treatment of immune-mediated disease. The MECA79 antibody recognizes peripheral node addressin molecules expressed by high endothelial venules of lymph nodes. By mimicking lymphocyte trafficking to the lymph nodes, we have engineered MECA79-coated microparticles containing an immunosuppressive medication, tacrolimus. Following intravenous administration, MECA79-bearing particles showed marked accumulation in the draining lymph nodes of transplanted animals. Using an allograft heart transplant model, we show that targeted lymph node delivery of microparticles containing tacrolimus can prolong heart allograft survival with negligible changes in tacrolimus serum level. Using MECA79 conjugation, we have demonstrated targeted delivery of tacrolimus to the lymph nodes following systemic administration, with the capacity for immune modulation in vivo.
authors.affiliation: Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Jamil
authors.initials: J
authors.lastname: Azzi
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61820, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Yin
authors.affiliation: Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Mayuko
authors.initials: M
authors.lastname: Uehara
authors.affiliation: Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Ohori
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61820, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Tang
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61820, USA.
authors.forename: Kaimin
authors.initials: K
authors.lastname: Cai
authors.affiliation: Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Takaharu
authors.initials: T
authors.lastname: Ichimura
authors.affiliation: Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Martina
authors.initials: M
authors.lastname: McGrath
authors.affiliation: Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Omar
authors.initials: O
authors.lastname: Maarouf
authors.affiliation: Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Eirini
authors.initials: E
authors.lastname: Kefaloyianni
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Loughhead
authors.affiliation: Department of Pathology, Clinical Laboratories Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Jarolim
authors.initials: J
authors.lastname: Petr
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61820, USA.
authors.forename: Qidi
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61820, USA.
authors.forename: Mincheol
authors.initials: M
authors.lastname: Kwon
authors.affiliation: Division of Transplant Surgery and Transplant Surgery Research Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: Tullius
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA; The Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
authors.forename: Ulrich H
authors.initials: UH
authors.lastname: von Andrian
authors.affiliation: Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61820, USA. Electronic address: jianjunc@illinois.edu.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: rabdi@rics.bwh.harvard.edu.
authors.forename: Reza
authors.initials: R
authors.lastname: Abdi
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000954:Antigens, Surface / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D006085:Graft Survival / Q000187:drug effects; D016027:Heart Transplantation; D007155:Immunologic Factors / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008198:Lymph Nodes / Q000187:drug effects / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008863:Microspheres; D009368:Neoplasm Transplantation; D011091:Polyesters / Q000737:chemistry; D016559:Tacrolimus / Q000494:pharmacology
chemical_list: D000906:Antibodies; D000954:Antigens, Surface; D016207:Cytokines; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; C069886:L-selectin counter-receptors; D008565:Membrane Proteins; D011091:Polyesters; C033616:poly(lactide); D016559:Tacrolimus