title: A novel approach to cancer immunotherapy: tumor cells decorated with CD80 generate effective antitumor immunity.
abstract: Malignant cells often elude the immune system by lacking costimulatory signals required for the generation of effective antitumor immunity. Immunization with tumor cells genetically modified to express costimulatory molecules is a highly promising approach to cancer immunotherapy. However, genetic modification of tumor cells is not only labor/time intensive but is also less efficient and bears safety concerns. To override these complications, we have recently developed a novel technology that allows for efficient and durable display of exogenous proteins on the surface of a cell within 2 h. This technology involves modification of the cell membrane with a biotin derivative and decoration of biotinylated cells with proteins chimeric with core streptavidin. A chimeric molecule composed of the extracellular domains of the human CD80 costimulatory molecule and core streptavidin (CD80-SA) was efficiently displayed on the cell surface, where it persisted with a t(1/2) of >10 days in vivo. Tumors from patients with advanced stage gynecologic cancers decorated with CD80-SA elicited potent ex vivo tumor-specific proliferative and cytotoxic responses in autologous lymphocytes. Immunization with tumor cells decorated with CD80-SA completely prevented tumor growth in an aggressive model of mouse lymphoma. This technology may serve as a fast, efficient, and safe alternative to gene transfer approaches for engineering tumor cells for use in immunotherapy and research.
authors.affiliation: Institute for Cellular Therapeutics, University of Louisville, Louisville, Kentucky 40202, USA.
authors.forename: Narendra P
authors.initials: NP
authors.lastname: Singh
authors.forename: Esma S
authors.initials: ES
authors.lastname: Yolcu
authors.forename: Douglas D
authors.initials: DD
authors.lastname: Taylor
authors.forename: Cicek
authors.initials: C
authors.lastname: Gercel-Taylor
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Metzinger
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Dreisbach
authors.forename: Haval
authors.initials: H
authors.lastname: Shirwan
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001710:Biotin / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D005260:Female; D018014:Gene Transfer Techniques; D005833:Genital Neoplasms, Female / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008213:Lymphocyte Activation; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000517:prevention & control / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019809:Streptavidin / Q000031:analogs & derivatives* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D018122:B7-1 Antigen; D011993:Recombinant Fusion Proteins; D001710:Biotin; D019809:Streptavidin