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Targeting high-grade B cell lymphoma with CD19-specific T cells

Item Type:Article
Title:Targeting high-grade B cell lymphoma with CD19-specific T cells
Creators Name:Lehmann, F.M. and Maurberger, A. and Feicht, S. and Helm, F. and Ladinig, C. and Kieback, E. and Uckert, W. and Kammertöns, T. and Kremmer, E. and Mautner, J. and Gerbitz, A. and Bornkamm, G.W.
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.
Keywords:B Cell Lymphoma, CD19, CD4 T Cell, T Cell Therapy, Animals, Mice
Source:International Journal of Cancer
Page Range:1153-1164
Date:1 September 2014
Official Publication:https://doi.org/10.1002/ijc.28760
PubMed:View item in PubMed

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