title: Targeting high-grade B cell lymphoma with CD19-specific T cells.
abstract: Adoptive T cell therapy is an important additional treatment option for malignant diseases resistant to chemotherapy. Using a murine high-grade B cell lymphoma model, we have addressed the question whether the B cell differentiation antigen CD19 can act as rejection antigen. CD19(-/-) mice inoculated with CD19(+) B cell lymphoma cells showed higher survival rates than WT mice and were protected against additional tumor challenge. T cell depletion prior to tumor transfer completely abolished the protective response. By heterotypic vaccination of CD19(-/-) mice against murine CD19, survival after tumor challenge was significantly increased. To define protective epitopes within the CD19 molecule, T cells collected from mice that had survived the tumor transfer were analyzed for IFNγ secretion in response to CD19-derived peptides. The majority of mice exhibited a CD4(+) T cell response to CD19 peptide 27, which was the most dominant epitope after CD19 vaccination. A peptide 27-specific CD4(+) T cell line protected CD19(-/-) mice against challenge with CD19(+) lymphoma and also cured a significant proportion of WT mice from recurrent disease in a model of minimal residual disease after chemotherapy. In conclusion, our data highlight CD19-specific CD4(+) T cells for adoptive T cell therapy of B cell lymphomas.
authors: Institute of Clinical Molecular Biology and Tumor Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich, Germany.
authors: Frank M
authors: FM
authors: Lehmann
authors: Anna
authors: A
authors: Maurberger
authors: Samantha
authors: S
authors: Feicht
authors: Florian
authors: F
authors: Helm
authors: Camilla
authors: C
authors: Ladinig
authors: Elisa
authors: E
authors: Kieback
authors: Wolfgang
authors: W
authors: Uckert
authors: Thomas
authors: T
authors: Kammertöns
authors: Elisabeth
authors: E
authors: Kremmer
authors: Josef
authors: J
authors: Mautner
authors: Armin
authors: A
authors: Gerbitz
authors: Georg W
authors: GW
authors: Bornkamm
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008212:Lymphocyte Depletion; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured
chemical_list: D018941:Antigens, CD19; D007371:Interferon-gamma
keywords: B cell lymphoma; CD19; CD4 T cell; T cell therapy