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

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Item Type:	Article
Title:	Targeting high-grade B cell lymphoma with CD19-specific T cells
Creators Name:	Lehmann, F.M., Maurberger, A., Feicht, S., Helm, F., Ladinig, C., Kieback, E., Uckert, W., Kammertöns, T., Kremmer, E., Mautner, J., 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
ISSN:	0020-7136
Publisher:	Wiley-Blackwell
Volume:	135
Number:	5
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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