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. 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. © 2014 UICC.