TY - JOUR
T1 - Novel myeloperoxidase-derived HLA-A2-restricted peptides as therapeutic targets against myeloid leukemia
AU - Lu, Sijie
AU - Tallis, Eran
AU - Ding, Xiaoling
AU - Li, Dan
AU - Cox, Kathryn
AU - You, M. James
AU - St John, Lisa
AU - Alatrash, Gheath
AU - Ma, Qing
AU - Molldrem, Jeffrey J.
N1 - Funding Information:
This study was supported by the National Cancer Institute (JJM and KC; 5P50CA100632-05 and P30CA16672, respectively). The manuscript was edited by The University of Texas MD Anderson Cancer Center Research Medical Library.
Funding Information:
This study was supported by the National Cancer Institute (JJM and KC; 5P50CA100632-05 and P30CA16672, respectively). The manuscript was edited by The University of Texas MD Anderson Cancer Center Research Medical Library. Conception and design of the study: SL, ET, QM and JJM. Acquisition of data: SL, ET, XD, DL, KC and QM. Analysis and interpretation of data: SL, ET, XD, DL, KC, QM and MJY. Drafting or revising the manuscript: LS, GA, SL, ET, QM and JJM. All authors have approved the final article.
Publisher Copyright:
© 2021 International Society for Cell & Gene Therapy
PY - 2021/9
Y1 - 2021/9
N2 - 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.
AB - 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.
KW - HLA-A2-restricted peptide
KW - cytotoxic T lymphocytes
KW - leukemia-associated antigen
KW - myeloperoxidase
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U2 - 10.1016/j.jcyt.2021.05.003
DO - 10.1016/j.jcyt.2021.05.003
M3 - Article
C2 - 34215503
AN - SCOPUS:85108946598
SN - 1465-3249
VL - 23
SP - 793
EP - 798
JO - Cytotherapy
JF - Cytotherapy
IS - 9
ER -