title: Development and application of CD19-specific T cells for adoptive immunotherapy of B cell malignancies.
abstract: The graft-versus-leukemia (GVL)-effect achieved by donor-derived T cells arising from transplanted allogeneic hematopoietic stem cells or given as donor-leukocyte infusions (DLI) after allogeneic transplant, demonstrates that donor-derived T cells can eradicate B-lineage malignancies. However, graft-versus-host-disease (GVHD) occurring after allogeneic hematopoietic stem-cell transplant (HSCT) or polyclonal DLI can limit the efficacy of these interventions. This toxicity can be avoided by using autologous T cells and/or tumor-specific cytotoxic T lymphocytes (CTLs). To generate antigen-specific T cells that can be derived from the allogeneic donor or the patient, we have genetically manipulated T cells to express a CD19-specific chimeric immunoreceptor. This renders T cells specific for CD19, a cell surface molecule found on B-lineage leukemia and lymphoma. This review will demonstrate the redirected specificity of CD19-specific T cells and implementation of clinical trials using these cellular agents.
authors.affiliation: Division of Hematology and Hematopoietic Cell Transplantation Transplant, Beckman Research Institute and City of Hope National Medical Center, Duarte, CA 91010-3000, USA. lcooper@coh.org
authors.forename: Laurence J N
authors.initials: LJ
authors.lastname: Cooper
authors.forename: Zaid
authors.initials: Z
authors.lastname: Al-Kadhimi
authors.forename: David
authors.initials: D
authors.lastname: DiGiusto
authors.forename: Michael
authors.initials: M
authors.lastname: Kalos
authors.forename: David
authors.initials: D
authors.lastname: Colcher
authors.forename: Andrew
authors.initials: A
authors.lastname: Raubitschek
authors.forename: Steve J
authors.initials: SJ
authors.lastname: Forman
authors.forename: Michael C
authors.initials: MC
authors.lastname: Jensen
mesh_terms: D018941:Antigens, CD19 / Q000276:immunology; D020544:Graft vs Leukemia Effect; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D015448:Leukemia, B-Cell / Q000628:therapy*; D016393:Lymphoma, B-Cell / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation
chemical_list: D018941:Antigens, CD19