Development and application of CD19-specific T cells for adoptive immunotherapy of B cell malignancies.
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.
Cooper
Laurence J N
LJ
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
Al-Kadhimi
Zaid
Z
DiGiusto
David
D
Kalos
Michael
M
Colcher
David
D
Raubitschek
Andrew
A
Forman
Steve J
SJ
Jensen
Michael C
MC
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
D018941:Antigens, CD19