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Prepublished online as a Blood First Edition Paper on October 10, 2002; DOI 10.1182/blood-2002-07-1989. This Article Full Text (PDF) All Versions of this Article: 2002-07-1989v1 101/4/1637    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Cooper, L. J N Articles by Jensen, M. C Search for Related Content PubMed PubMed Citation Articles by Cooper, L. J N Articles by Jensen, M. C Social Bookmarking                   What's this? Submitted July 5, 2002 Accepted September 27, 2002 T-CELL CLONES CAN BE RENDERED SPECIFIC FOR CD19: TOWARD THE SELECTIVE AUGMENTATION OF THE GRAFT VERSUS B-LINEAGE LEUKEMIA EFFECT Laurence J N Cooper*, Max S Topp, Lisa Marie A Serrano, Sergio Gonzalez, Wen-Chung Chang, Araceli Naranjo, Christine L Wright, Leslie Popplewell, Andrew Raubitschek, Stephen J Forman, and Michael C Jensen Division of Pediatric Hematology-Oncology, City of Hope National Medical Center, Duarte, CA, USA Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Hematology, Oncology, Rheumatology and Immunology, University Hospital Tubingen, Tuebingen, Germany Division of Molecular Medicine, Beckman Research Institute, Duarte, CA, USA Division of Hematology and Bone Marrow Transplantation, City of Hope National Medical, Duarte, CA, USA Department of Radioimmunotherapy, CenterCity of Hope National Medical Center, Duarte, CA, USA * Corresponding author; email: lcooper{at}coh.org. Relapse of B-lineage acute lymphoblastic leukemia (B-ALL) after allogeneic hematopoietic stem-cell transplant (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-specific T-cell clones is a conceptually attractive strategy to decrease relapse rates without exacerbating graft-versus-host disease (GVHD). Towards this end, we investigated whether a genetic engineering approach could render CD8+ cytotoxic T lymphocytes (CTL) specific for tumor cells that express the B-cell lineage cell-surface molecule CD19. This was accomplished by the genetic modification of CTL to express a chimeric immunoreceptor composed of a CD19-specific single chain immunoglobulin extracellular targeting domain fused to a CD3- intracellular signaling domain. CD19-redirected CTL-clones display potent CD19-specific lytic activity and chimeric immunoreceptor-regulated cytokine production and proliferation. Since B-ALL cells can evade T-cell/NK-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+ CTL towards CD19+ cells with disparate levels of ICAM-1, LFA-1, and LFA-3. We observed that recognition of B-lineage tumor lines by CD19-specific CTL 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 CTL could lyse primary B-ALL blasts. 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