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Immunogenicity of recurrent mutations in MYD88 and EZH2 in non-Hodgkin lymphomas
  1. Julie S Nielsen1,
  2. Andrew R Chang1,
  3. Darin A Wick1,
  4. Colin G Sedgwick1,
  5. Zusheng Zong2,
  6. Andrew J Mungall3,
  7. Bemuluyigza Baraki2,
  8. Natalie Kinloch2,
  9. Zabrina L Brumme2,
  10. Steven P Treon4,
  11. Joseph M Connors3,
  12. Randy D Gascoyne3,
  13. John R Webb1,
  14. Brian R Berry5,
  15. Ryan D Morin2,
  16. Nicol Macpherson1 and
  17. Brad H Nelson1
  1. Aff1 grid.248762.d0000000107023000BC Cancer Agency Victoria BC Canada
  2. Aff2 grid.61971.380000000419367494Simon Fraser University Burnaby BC Canada
  3. Aff3 grid.248762.d0000000107023000BC Cancer Agency Vancouver BC Canada
  4. Aff4 grid.65499.370000000121069910Dana-Farber Cancer Institute Boston MA USA
  5. Aff5 grid.17091.3e0000000122889830University of British Columbia Vancouver BC Canada

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Meeting abstracts

A fundamental challenge in cancer genomics is to design effective, personalized treatments based on the mutational profiles of tumors. Pharmacological targeting of the numerous aberrant pathways found in individual tumors remains exceedingly challenging, but T cell-based therapies are an attractive alternative because of the enormous diversity and exquisite specificity of antigen recognition. We assessed the immunogenicity of three common driver mutations in human lymphoma – MYD88L265P, EZH2Y641N, and EZH2Y641F – to evaluate their suitability as targets for immunotherapy. Antigen presenting cells were loaded with overlapping peptide libraries containing each mutation and used to stimulate autologous T cells from healthy donors and lymphoma patients. Stimulated T cells were screened by interferon-gamma ELISPOT for reactivity to mutant versus wildtype peptides as well as full-length proteins. All three peptide libraries elicited T cell responses from multiple donors representing diverse HLA haplotypes. Moreover, we identified peptides from MYD88L265P and EZH2Y641N that were naturally processed and presented, and the corresponding T cell responses were specific for mutant proteins. Thus, MYD88L265P and EZH2Y641N both represent compelling antigens for immunotherapy of lymphoma patients. Funding was provided by the BC Cancer Foundation, the Canadian Cancer Society, and the Waldenstrom's Macroglobulinemia Foundation of Canada.