CD20 alternative splicing isoform generates immunogenic CD4 helper T epitopes.

Abstract

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.

• Authors: Charline Vauchy, Clementine Gamonet, Christophe Ferrand, Etienne Daguindau, Jeanne Galaine, Laurent Beziaud, Adrien Chauchet, Carole J Henry Dunand, Marina Deschamps, Pierre Simon Rohrlich, Christophe Borg, Olivier Adotevi, Yann Godet
• Journal: International journal of cancer (Int J Cancer) Vol. 137 Issue 1 Pg. 116-26 (Jul 01 2015) ISSN: 1097-0215 [Electronic] United States
• PMID: 25449106 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 UICC.

Chemical References

• Antigens, CD20
• Antigens, Neoplasm
• Epitopes, T-Lymphocyte
• Peptides
• Protein Isoforms

Topics

• Alternative Splicing
• Animals
• Antigens, CD20 (genetics, immunology)
• Antigens, Neoplasm (genetics, immunology)
• Cell Line, Tumor
• Epitopes, T-Lymphocyte (immunology)
• Humans
• Immunization
• Lymphoma, B-Cell (genetics, immunology, therapy)
• Mice
• Mice, Transgenic
• Peptides (administration & dosage, immunology)
• Protein Isoforms (genetics, metabolism)
• T-Lymphocytes, Helper-Inducer (immunology)