Injectable dendritic cell-carrying alginate gels for immunization and immunotherapy.
Dendritic cell vaccines, in which antigen-loaded dendritic cells (DCs) are injected directly into patients to trigger immune responses, are in development as a treatment for cancer and some infectious diseases. In this study, we tested the concept of delivering DCs in an injectable hydrogel matrix, with the aim of harboring dendritic cells for prolonged time periods at a defined site and trapping/concentrating factors secreted by DCs to establish an inflammatory milieu in situ. To achieve these goals, a self-gelling formulation of alginate was developed, obtained by mixing calcium-loaded alginate microspheres with soluble alginate solution and dendritic cells, a formulation that rapidly gelled in vivo. When injected subcutaneously in mice, these alginate 'vaccination nodes' containing activated DCs attracted both host dendritic cells and a large number of T cells to the injection sites over a week in vivo, while some of the inoculated DCs trafficked to the draining lymph nodes. Using an adoptive transfer model to track a defined population of T cells responding to immunization with antigen-loaded DCs, we show that DC/alginate immunization led to recruitment of activated antigen-specific T cells to the alginate matrix, in a manner dependent on the presence of the DCs. This gel/DC immunization system may thus be of interest for immunotherapy to direct the accumulation of immune cells at solid tumors or infection sites in the presence of supporting factors co-delivered by the hydrogel matrix.
Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States.
Yuki
Y
Hori
Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States.
Amy M
AM
Winans
Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States.
Catherine C
CC
Huang
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, United States.
Elizabeth M
EM
Horrigan
Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States.
Darrell J
DJ
Irvine
D000464:Alginates; D000818:Animals; D003713:Dendritic Cells; D005434:Flow Cytometry; D005782:Gels; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D007167:Immunotherapy; D051379:Mice; D008810:Mice, Inbred C57BL; D014612:Vaccines / Q000008:administration & dosage*
D000464:Alginates; D005782:Gels; D006603:Hexuronic Acids; D014612:Vaccines; D020723:Glucuronic Acid