{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T10:03:26Z","timestamp":1792058606080,"version":"4.4.0"},"reference-count":63,"publisher":"American Society of Hematology","issue":"4","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,2,15]]},"abstract":"<jats:p>Relapse of B-lineage acute lymphoblastic leukemia (B-ALL) after allogeneic hematopoietic stem cell transplantation (HSCT) commonly results from the failure of a graft-versus-leukemia (GVL) effect to eradicate minimal residual disease. Augmenting the GVL effect by the adoptive transfer of donor-derived B-ALL\u2013specific T-cell clones is a conceptually attractive strategy to decrease relapse rates without exacerbating graft-versus-host disease (GVHD). Toward this end, we investigated whether a genetic engineering approach could render CD8+ cytotoxic T lymphocytes (CTLs) specific for tumor cells that express the B-cell lineage cell surface molecule CD19. This was accomplished by the genetic modification of CTLs to express a chimeric immunoreceptor composed of a CD19-specific single-chain immunoglobulin extracellular targeting domain fused to a CD3-\u03b6 intracellular signaling domain. CD19-redirected CTL clones display potent CD19-specific lytic activity and chimeric immunoreceptor-regulated cytokine production and proliferation. Because B-ALL cells can evade T-cell\/natural killer- cell recognition by down-regulation of cell surface accessory molecules that participate in the formation of a functional immunologic synapse, we compared the CD19-specific effector function of genetically modified CD8+ CTLs toward CD19+ cells with disparate levels of intercellular adhesion molecule 1 (ICAM-1), leukocyte function-associated antigen 1 (LFA-1), and LFA-3. We observed that recognition of B-lineage tumor lines by CD19-specific CTLs was not impaired by low levels of ICAM-1, LFA-1, and LFA-3 cell surface expression, a functional attribute that is likely a consequence of our high-affinity CD19-specific chimeric immunoreceptor. Furthermore, the CD19-specific CTLs could lyse primary B-ALL blasts. These preclinical observations form the basis for implementing clinical trials using donor-derived CD19-specific T-cell clones to treat or prevent relapse of B-ALL after allogeneic HSCT.<\/jats:p>","DOI":"10.1182\/blood-2002-07-1989","type":"journal-article","created":{"date-parts":[[2003,1,30]],"date-time":"2003-01-30T21:36:12Z","timestamp":1043962572000},"page":"1637-1644","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":218,"title":["T-cell clones can be rendered specific for CD19: toward the selective augmentation of the graft-versus-B\u2013lineage leukemia effect"],"prefix":"10.1182","volume":"101","author":[{"given":"Laurence J. N.","family":"Cooper","sequence":"first","affiliation":[{"name":"From the Divisions of Pediatric Hematology\/Oncology, Molecular Medicine and Hematology and Bone Marrow Transplant, and Department of Radioimmunotherapy, Beckman Research Institute and City of Hope National Medical Center, Duarte, CA; and Fred Hutchinson Cancer Research Center, Division of Clinical Research, Seattle, WA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max S.","family":"Topp","sequence":"additional","affiliation":[{"name":"From the Divisions of Pediatric Hematology\/Oncology, Molecular Medicine and Hematology and Bone Marrow Transplant, and Department of Radioimmunotherapy, Beckman Research Institute and City of Hope National Medical Center, Duarte, CA; and Fred Hutchinson Cancer Research Center, Division of Clinical Research, Seattle, WA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa Marie","family":"Serrano","sequence":"additional","affiliation":[{"name":"From the 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Radioimmunotherapy, Beckman Research Institute and City of Hope National Medical Center, Duarte, CA; and Fred Hutchinson Cancer Research Center, Division of Clinical Research, Seattle, WA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie","family":"Popplewell","sequence":"additional","affiliation":[{"name":"From the Divisions of Pediatric Hematology\/Oncology, Molecular Medicine and Hematology and Bone Marrow Transplant, and Department of Radioimmunotherapy, Beckman Research Institute and City of Hope National Medical Center, Duarte, CA; and Fred Hutchinson Cancer Research Center, Division of Clinical Research, Seattle, WA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Raubitschek","sequence":"additional","affiliation":[{"name":"From the Divisions of Pediatric Hematology\/Oncology, Molecular Medicine and Hematology and Bone Marrow Transplant, and Department of Radioimmunotherapy, Beckman Research Institute and City of Hope 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