Details

Autor(en) / Beteiligte

• Lehmann, Frank M.
• Maurberger, Anna
• Feicht, Samantha
• Helm, Florian
• Ladinig, Camilla
• Kieback, Elisa
• Uckert, Wolfgang
• Kammertöns, Thomas
• Kremmer, Elisabeth
• Mautner, Josef
• Gerbitz, Armin
• Bornkamm, Georg W.

Titel

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

Ist Teil von

• International journal of cancer, 2014-09, Vol.135 (5), p.1153-1164

Ort / Verlag

United States: Wiley Subscription Services, Inc

Erscheinungsjahr

2014

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• 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. What's new? While adoptive T cell transfer has evolved as a promising approach to treat therapy‐resistant cancers, finding the right target antigen can be challenging. Here, the authors identify the cell‐surface marker CD19 as a rejection antigen in murine high‐grade B‐cell malignancies. They further show that CD4+ T cells play an essential role in tumor rejection in their disease model, thus underscoring the key function of these cells in adoptive T‐cell therapy.