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Int J Cancer. 2015 Jul 1;137(1):116-26. doi: 10.1002/ijc.29366. Epub 2014 Dec 12.

CD20 alternative splicing isoform generates immunogenic CD4 helper T epitopes.

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INSERM UMR1098, F25020 Besançon cedex, France; Université de Franche-Comté, F25020 Besançon cedex, France; EFS Bourgogne Franche-Comté, F25020 Besançon cedex, France.


Cancer-specific splice variants gain significant interest as they generate neo-antigens that could be targeted by immune cells. CD20, a membrane antigen broadly expressed in mature B cells and in B cell lymphomas, is subject to an alternative splicing named D393-CD20 leading to loss of membrane expression of the spliced isoform. D393-CD20 expression is detectable in transformed B cells and upregulated in various lymphoma B cells. In this study, we show that D393-CD20 is translated in malignant B cells and that D393-CD20 specific CD4 T cells producing IFN-γ are present in B-cell lymphoma patients. Then, we have investigated whether the 20mer D393-CD20 peptide spanning the splicing site might be targeted by the immune system and we have shown that D393-CD20-specific CD4 Th1 clones could directly recognize malignant B cell lines and kill autologous lymphoma B cells indicating that D393-CD20-derived epitopes are naturally processed and presented on tumor cells. Finally, D393-CD20 peptide-based vaccination induced specific CD8 and CD4 T cell responses in HLA-humanized transgenic mice suggesting the presentation of D393-CD20 derived peptides on both HLA Class-I and -II. These findings support further investigations on the potential use of D393-CD20 directed specific immunotherapy in B cell malignancies.


B-cell lymphoma; CD20 antigen; CD4 T cells; immunotherapy; splicing

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