Novel myeloperoxidase-derived HLA-A2-restricted peptides as therapeutic targets against myeloid leukemia

Sijie Lu, Eran Tallis, Xiaoling Ding, Dan Li, Kathryn Cox, M. James You, Lisa St John, Gheath Alatrash, Qing Ma, Jeffrey J. Molldrem

Research output: Contribution to journalArticlepeer-review

Abstract

Background aims: Human myeloperoxidase has been shown to be overexpressed in many types of leukemia, such as chronic myeloid leukemia, acute myeloid leukemia and myelodysplastic syndrome. The authors identified two myeloperoxidase-derived HLA-A2-restricted peptides, MY4 and MY8, as novel leukemia-associated antigens. Methods: Ex vivo-elicited MY4- and MY8-specific cytotoxic T lymphocytes were generated, and tested for leukemia cell lysis in vitro and in NOD/SCID AML xenograft model. Results: These MY4- and MY8-specific cytotoxic T lymphocytes killed leukemic blasts while sparing healthy donor bone marrow cells. In addition, co-injection of MY4- and MY8-specific cytotoxic T lymphocytes into nonobese diabetic/severe combined immunodeficiency mice with acute myeloid leukemia drastically reduced tumor burden in vivo. The authors also found that MY4- and MY8-specific T cells could be detected in the peripheral blood mononuclear cells of allogeneic stem cell transplant recipients. Conclusions: These antigen-specific T cells were significantly increased in blood samples from patients compared with healthy donors, suggesting that both MY4 and MY8 are immunogenic and that MY4- and MY8-specific cytotoxic T lymphocytes may play a role in reducing leukemia in vivo. Thus, the discovery of MY4 and MY8 as novel leukemia-associated antigens paves the way for targeting these antigens in immunotherapy against myeloid leukemia.

Original languageEnglish (US)
Pages (from-to)793-798
Number of pages6
JournalCytotherapy
Volume23
Issue number9
DOIs
StatePublished - Sep 2021

Keywords

  • HLA-A2-restricted peptide
  • cytotoxic T lymphocytes
  • leukemia-associated antigen
  • myeloperoxidase

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Genetics(clinical)
  • Cell Biology
  • Transplantation
  • Cancer Research

MD Anderson CCSG core facilities

  • Flow Cytometry and Cellular Imaging Facility
  • Clinical Trials Office
  • Research Animal Support Facility

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