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Manufacturing Chimeric Antigen Receptor (CAR) T Cells for Adoptive Immunotherapy
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Development and application of CD19-specific T cells for adoptive immunotherapy of B cell malignancies

Laurence J N Cooper1, Zaid Al-Kadhimi, David DiGiusto

  • 1Division 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

Blood Cells, Molecules & Diseases
|June 30, 2004
PubMed

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.

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