{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T02:36:08Z","timestamp":1761100568369},"reference-count":25,"publisher":"American Society of Hematology","issue":"2","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Successful stem cell transplantation (SCT) across HLA barriers can be performed with cord blood, megadoses of stem cells, or with nonmyeloablative conditioning strategies. Because the HLA-mismatched transplants are often T-cell depleted, leukemia relapse rates are high. Treatment of relapsed leukemia after HLA-mismatched SCT is difficult. A novel potential strategy to treat relapsed leukemia after HLA-mismatched SCT is the use of patients' mismatched HLA molecules as antigen-presenting molecules to generate hematopoietic system\u2013specific cytotoxic T cells (CTLs) from the stem cell donor. Adoptive transfer of these hematopoietic system\u2013specific CTLs that are restricted by nonself HLA molecules may eliminate leukemia without affecting the patient's nonhematopoietic cells or donor hematopoietic cells. We investigated the feasibility of this strategy using the hematopoietic system\u2013specific minor histocompatibility antigen HA-1, which is known to induce HLA-A2\u2013restricted CTLs. HLA-A2\u2212peripheral blood mononuclear cells were stimulated with HLA-A2+ T2 cells pulsed with synthetic HA-1 peptide or with dendritic cells transduced with the HA-1 cDNA. Tetrameric HLA-A2\/HA-1 peptide complexes were used to monitor and enrich HA-1\u2013specific CTLs. In the alloreactive cultures, HA-1\u2013specific CTLs were enriched up to 7% by 3 rounds of antigen-specific stimulations and up to 87% by fluorescence-activated cell sorting of tetramer-positive T cells. The HA-1\u2013specific CTLs showed specific lysis of the relevant target cells, including leukemic cells. Because the polyclonal CTL cultures also contained natural killer cells and allo\u2013HLA-A2\u2013specific CTLs, CTL clones were generated that showed the expected HA-1 specificity only. Thus, HA-1\u2013specific CTLs restricted by nonself HLA-A2 molecules can be generated in an HLA-A2\u2013mismatched setting.<\/jats:p>","DOI":"10.1182\/blood-2002-01-0024","type":"journal-article","created":{"date-parts":[[2002,10,11]],"date-time":"2002-10-11T18:33:52Z","timestamp":1034361232000},"page":"547-552","update-policy":"http:\/\/dx.doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":51,"title":["Generation of minor histocompatibility antigen HA-1\u2013specific cytotoxic T cells restricted by nonself HLA molecules: a potential strategy to treat relapsed leukemia after HLA-mismatched stem cell transplantation"],"prefix":"10.1182","volume":"100","author":[{"given":"Tuna","family":"Mutis","sequence":"first","affiliation":[{"name":"From the Department of Immunohematology and Blood Transfusion and the Department of Hematology, Leiden University Medical Center, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Els","family":"Blokland","sequence":"additional","affiliation":[{"name":"From the Department of Immunohematology and Blood Transfusion and the Department of Hematology, Leiden University Medical Center, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel","family":"Kester","sequence":"additional","affiliation":[{"name":"From the Department of Immunohematology and Blood Transfusion and the Department of Hematology, Leiden University Medical Center, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ellen","family":"Schrama","sequence":"additional","affiliation":[{"name":"From the Department of Immunohematology and Blood Transfusion and the Department of Hematology, Leiden University Medical Center, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Els","family":"Goulmy","sequence":"additional","affiliation":[{"name":"From the Department of Immunohematology and Blood Transfusion and the Department of Hematology, Leiden University Medical Center, The Netherlands."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"234","reference":[{"key":"2020021218390844700_B1","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1182\/blood.V75.3.555.555","article-title":"Graft-versus-leukemia reactions after bone marrow transplantation.","volume":"75","author":"Horowitz","year":"1990","journal-title":"Blood."},{"key":"2020021218390844700_B2","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1182\/blood.V86.5.2041.bloodjournal8652041","article-title":"Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients. 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