title: A CpG-loaded tumor cell vaccine induces antitumor CD4+ T cells that are effective in adoptive therapy for large and established tumors.
abstract: We designed a whole tumor cell vaccine by "loading" lymphoma tumor cells with CG-enriched oligodeoxynucleotide (CpG), a ligand for the Toll-like receptor 9 (TLR9). CpG-loaded tumor cells were phagocytosed, delivering both tumor antigen(s) and the immunostimulatory CpG molecule to antigen-presenting cells (APCs). These APCs then expressed increased levels of costimulatory molecules and induced T-cell immunity. TLR9 was required in the APCs but not in the CpG-loaded tumor cell. We demonstrate that T cells induced by this vaccine are effective in adoptive cellular therapy for lymphoma. T cells from vaccinated mice transferred into irradiated, syngeneic recipients protected against subsequent lymphoma challenge and, remarkably, led to regression of large and established tumors. This therapeutic effect could be transferred by CD4(+) but not by CD8(+) T cells. A CpG-loaded whole-cell vaccination is practical and has strong potential for translation to the clinical setting. It is currently being tested in a clinical trial of adoptive immunotherapy for mantle-cell lymphoma.
authors.affiliation: Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Goldstein
authors.forename: Bindu
authors.initials: B
authors.lastname: Varghese
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Brody
authors.forename: Ranjani
authors.initials: R
authors.lastname: Rajapaksa
authors.forename: Holbrook
authors.initials: H
authors.lastname: Kohrt
authors.forename: Debra K
authors.initials: DK
authors.lastname: Czerwinski
authors.forename: Shoshana
authors.initials: S
authors.lastname: Levy
authors.forename: Ronald
authors.initials: R
authors.lastname: Levy
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D018899:CpG Islands / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D016219:Immunotherapy, Adoptive; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D008223:Lymphoma / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010587:Phagocytosis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured; D014611:Vaccination
chemical_list: D019496:Cancer Vaccines