Induction of tumor-specific protective immunity by in situ Langerhans cell vaccine.
Although anti-tumor immunity is inducible by dendritic cell (DC)-based vaccines, time- and cost-consuming "customizing" processes required for ex vivo DC manipulation have hindered broader clinical applications of this concept. Epidermal Langerhans cells (LCs) migrate to draining lymph nodes and undergo maturational changes on exposure to reactive haptens. We entrapped these migratory LCs by subcutaneous implantation of ethylene-vinyl-acetate (EVA) polymer rods releasing macrophage inflammatory protein (MIP)-3beta (to create an artificial gradient of an LC-attracting chemokine) and topical application of hapten (to trigger LC emigration from epidermis). The entrapped LCs were antigen-loaded in situ by co-implantation of the second EVA rods releasing tumor-associated antigens (TAAs). Potent cytotoxic T-lymphocyte (CTL) activities and protective immunity against tumors were induced efficiently with each of three tested TAA preparations. Thus, tumor-specific immunity is inducible by the combination of LC entrapment and in situ LC loading technologies. Our new vaccine strategy requires no ex vivo DC manipulation and thus may provide time and cost savings.
Kumamoto
Tadashi
T
Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Huang
Eric K
EK
Paek
Hyun Joon
HJ
Morita
Akimichi
A
Matsue
Hiroyuki
H
Valentini
Robert F
RF
Takashima
Akira
A
D000818:Animals; D001709:Biotechnology / Q000191:economics; D001854:Bone Marrow Cells / Q000166:cytology; D019496:Cancer Vaccines; D002465:Cell Movement; D002478:Cells, Cultured; D054415:Chemokine CCL19; D019742:Chemokines, CC / Q000378:metabolism; D002633:Chemotaxis; D003713:Dendritic Cells / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D000078404:Epidermal Cells; D007515:Islets of Langerhans / Q000166:cytology*; D008024:Ligands; D008198:Lymph Nodes / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011108:Polymers / Q000737:chemistry; D011145:Polyvinyls / Q000737:chemistry; D011994:Recombinant Proteins / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism; D013997:Time Factors
D019496:Cancer Vaccines; C515461:Ccl19 protein, mouse; D054415:Chemokine CCL19; D019742:Chemokines, CC; D008024:Ligands; D011108:Polymers; D011145:Polyvinyls; D011994:Recombinant Proteins; C016438:ethylenevinylacetate copolymer