Targeted Delivery of Immunomodulators to Lymph Nodes

Jamil Azzi, Qian Yin, Mayuko Uehara, Shunsuke Ohori, Li Tang, Kaimin Cai, Takaharu Ichimura, Martina McGrath, Omar Maarouf, Eirini Kefaloyianni, Scott Loughhead, Jarolim Petr, Qidi Sun, Mincheol Kwon, Stefan Tullius, Ulrich H. von Andrian, Jianjun Cheng, Reza Abdi

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

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.

Original languageEnglish
Pages (from-to)1202-1213
Number of pages12
JournalCell Reports
Volume15
Issue number6
DOIs
StatePublished - May 10 2016

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