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Lehmann, F.M. ; Maurberger, A.* ; Feicht, S.* ; Helm, F.* ; Ladinig, C.* ; Kieback, E.* ; Uckert, W.* ; Kammertöns, T.* ; Kremmer, E. ; Mautner, J. ; Gerbitz, A.* ; Bornkamm, G.W.

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

Int. J. Cancer 135, 1153-1164 (2014)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords B Cell Lymphoma ; Cd19 ; Cd4 T Cell ; T Cell Therapy; Chimeric-antigen-receptor; Tumor Rejection; Metastatic Melanoma; Transplant Recipients; Cancer Regression; Engaging Antibody; Adoptive Transfer; Ifn-gamma; Leukemia; Stroma
ISSN (print) / ISBN 0020-7136
e-ISSN 1097-0215
Journal International Journal of Cancer
Quellenangaben Volume: 135, Issue: 5, Pages: 1153-1164 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Hoboken
Reviewing status Peer reviewed
Institute(s) Institute of Clinical Molecular Biology and Tumor Genetics (K.MOLBI)
Institute of Molecular Immunology (IMI)
CCG Pediatric Tumor Immunology (AGV-KPT)