title: N-dihydrogalactochitosan as a potent immune activator for dendritic cells.
abstract: Immunotherapy has become one of the fastest growing areas of cancer research. A promising in situ autologous cancer vaccine (inCVAX) uses a novel immune activator, N-dihydrogalactochitosan (GC), that possesses the ability to stimulate dendritic cells (DC). inCVAX is a combination treatment procedure involving treatment of the tumor with a thermal near-infrared laser to liberate whole cell tumor antigens, followed by injection of GC (a glucosamine polymer with galactose attached to the amino groups) into the treated tumor thereby inducing a systemic antitumor immune response. Regression of both the treated tumor and distant untreated metastases has been observed in both nonclinical and clinical settings following inCVAX. We studied the stimulatory action of GC on relatively immature DCs (DC2.4 cell line) in vitro. GC at 1 mg/mL was a potent stimulator for DC with limited toxicity, giving increased expression of major histocompatibility complex class 2, CD80, and CD11c. Confocal imaging also revealed qualitatively increased uptake of antigen (Texas red-labeled ovalbumin) by DCs after the introduction of GC. To visualize cellular uptake, GC was conjugated with FITC-fluorophore revealing its cellular internalization after 8 hours. In some cases GC was more effective than the toxic TLR4 agonist, lipopolysaccharide. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 963-972, 2017.
authors.affiliation: Massachusetts General Hospital, Wellman Center for Photomedicine, Boston, Massachusetts 02114.|Department of Dermatology, Harvard Medical School, Boston, Massachusetts 02115.|The National Institute of Laser Enhanced Science, Cairo University, Cairo, Egypt.
authors.forename: Ahmed
authors.initials: A
authors.lastname: El-Hussein
authors.affiliation: Immunophotonics, Inc, 4320 Forest Park Ave, Suite #303, St. Louis, Missouri 63108.
authors.forename: Samuel S K
authors.initials: SSK
authors.lastname: Lam
authors.affiliation: Immunophotonics, Inc, 4320 Forest Park Ave, Suite #303, St. Louis, Missouri 63108.
authors.forename: Joseph
authors.initials: J
authors.lastname: Raker
authors.affiliation: University of Central Oklahoma, 100 N University Dr, Edmond, Oklahoma 73034.
authors.forename: Wei R
authors.initials: WR
authors.lastname: Chen
authors.affiliation: Massachusetts General Hospital, Wellman Center for Photomedicine, Boston, Massachusetts 02114.|Department of Dermatology, Harvard Medical School, Boston, Massachusetts 02115.|Harvard-MIT Division of Health Sciences and Technology, Cambridge, Massachusetts 02139.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hamblin
mesh_terms: D018122:B7-1 Antigen / Q000276:immunology; D039521:CD11c Antigen / Q000276:immunology; D002460:Cell Line; D048271:Chitosan / Q000031:analogs & derivatives / Q000494:pharmacology; D003713:Dendritic Cells / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D004306:Dose-Response Relationship, Immunologic; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000276:immunology
chemical_list: D018122:B7-1 Antigen; D039521:CD11c Antigen; D000949:Histocompatibility Antigens Class II; D007155:Immunologic Factors; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D048271:Chitosan
keywords: MHC II; N-dihydrogalactochitosan; confocal microscope; dendritic cells; flow cytometry; glycated chitosan; in situ cancer vaccine; inCVAX