Sijie Lu1, Eran Tallis1, Xiaoling Ding1, Dan Li1, Kathryn Cox1, M James You2, Lisa St John1, Gheath Alatrash1, Qing Ma1, Jeffrey J Molldrem3. 1. Department of Hematopoietic Biology and Malignancy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 2. Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 3. Department of Hematopoietic Biology and Malignancy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. Electronic address: jmolldre@mdanderson.org.
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.
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.
Authors: Qing Ma; Changqing Wang; Dan Jones; Kathryn E Quintanilla; Dan Li; Yang Wang; Eric D Wieder; Karen Clise-Dwyer; Gheath Alatrash; You Mj; Mark F Munsell; Sijie Lu; Muzaffar H Qazilbash; Jeffrey J Molldrem Journal: Cytotherapy Date: 2010-08-24 Impact factor: 5.414
Authors: Ilaria Bellantuono; Liquan Gao; Suzanne Parry; Steve Marley; Francesco Dazzi; Jane Apperley; John M Goldman; Hans J Stauss Journal: Blood Date: 2002-11-15 Impact factor: 22.113
Authors: Seymour J Klebanoff; Anthony J Kettle; Henry Rosen; Christine C Winterbourn; William M Nauseef Journal: J Leukoc Biol Date: 2012-10-11 Impact factor: 4.962
Authors: Shraddha Kumari; Sébastien Wälchli; Lars-Egil Fallang; Weiwen Yang; Fridtjof Lund-Johansen; Ton N Schumacher; Johanna Olweus Journal: Proc Natl Acad Sci U S A Date: 2013-12-16 Impact factor: 11.205
Authors: R Klar; S Schober; M Rami; S Mall; J Merl; S M Hauck; M Ueffing; A Admon; J Slotta-Huspenina; M Schwaiger; S Stevanović; R A J Oostendorp; D H Busch; C Peschel; A M Krackhardt Journal: Leukemia Date: 2014-04-16 Impact factor: 11.528