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CD20 alternative splicing isoform generates immunogenic CD4 helper T epitopes

Charline Vauchy1, Clementine Gamonet, Christophe Ferrand

  • 1INSERM UMR1098, F25020 Besançon cedex, France; Université de Franche-Comté, F25020 Besançon cedex, France; EFS Bourgogne Franche-Comté, F25020 Besançon cedex, France.

International Journal of Cancer
|December 3, 2014
PubMed

Insights

Cancer splice variants like D393-CD20 create neo-antigens for targeted immunotherapy. This study found D393-CD20 specific T cells in lymphoma patients, suggesting its potential for treating B cell malignancies.

Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • Cancer-specific splice variants are emerging targets for cancer immunotherapy due to neo-antigen generation.
  • CD20, a B cell marker, undergoes alternative splicing (D393-CD20), resulting in loss of membrane expression and potential for immune targeting.

Purpose of the Study:

  • To investigate the translation and immunogenicity of the D393-CD20 splice variant in B cell lymphomas.
  • To evaluate the potential of D393-CD20-derived epitopes for cancer immunotherapy.

Main Methods:

  • Detection of D393-CD20 translation in malignant B cells.
  • Identification and characterization of D393-CD20 specific CD4 T cell responses (IFN-γ production) in lymphoma patients.
  • Assessment of D393-CD20-specific CD4 Th1 clone recognition and killing of tumor cells.
  • Evaluation of D393-CD20 peptide-based vaccination in HLA-humanized transgenic mice.

Main Results:

  • D393-CD20 is translated in malignant B cells, and specific CD4 T cells are present in B-cell lymphoma patients.
  • D393-CD20-specific CD4 Th1 clones recognize and kill malignant B cell lines and autologous lymphoma cells.
  • Vaccination with D393-CD20 peptide elicits CD8 and CD4 T cell responses in mice, indicating presentation on HLA Class-I and -II.

Conclusions:

  • D393-CD20-derived epitopes are naturally processed and presented on tumor cells.
  • The D393-CD20 splice variant holds promise as a target for specific immunotherapy in B cell malignancies.
Keywords:
B-cell lymphomaCD20 antigenCD4 T cellsimmunotherapysplicing

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