Development and application of CD19-specific T cells for adoptive immunotherapy of B cell malignancies

Laurence J.N. Cooper; Zaid Al-Kadhimi; David DiGiusto; Michael Kalos; David Colcher; Andrew Raubitschek; Steve J. Forman; Michael C. Jensen

doi:10.1016/j.bcmd.2004.03.003

Development and application of CD19-specific T cells for adoptive immunotherapy of B cell malignancies

Laurence J.N. Cooper, Zaid Al-Kadhimi, David DiGiusto, Michael Kalos, David Colcher, Andrew Raubitschek, Steve J. Forman, Michael C. Jensen

Research output: Contribution to journal › Article › peer-review

42 Scopus citations

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.

Original language	English (US)
Pages (from-to)	83-89
Number of pages	7
Journal	Blood Cells, Molecules, and Diseases
Volume	33
Issue number	1
DOIs	https://doi.org/10.1016/j.bcmd.2004.03.003
State	Published - Jul 1 2004
Externally published	Yes

Keywords

Leukemia
T cell
Toxicity

ASJC Scopus subject areas

Molecular Medicine
Molecular Biology
Hematology
Cell Biology

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10.1016/j.bcmd.2004.03.003

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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.",

keywords = "Leukemia, T cell, Toxicity",

author = "Cooper, {Laurence J.N.} and Zaid Al-Kadhimi and David DiGiusto and Michael Kalos and David Colcher and Andrew Raubitschek and Forman, {Steve J.} and Jensen, {Michael C.}",

note = "Funding Information: Some of this information was presented at the 2003 2nd Annual Rebecca Miriam Guzner Memorial Symposium held at the City of Hope in Duarte California and this review is dedicated to the memory of Rebecca who succumbed to neuroblastoma in July 2000 at the age of 4. Support for the development and clinical application of CD19-specific T cells has been obtained from CA30206, CA33572, The Altschul Foundation, The Abe and Estelle Sanders Foundations, The Amy Phillips Charitable Foundation, The Leukemia and Lymphoma Society, Pediatric Cancer Research Foundation, The Sidney Kimmel Foundation for Cancer Research, The Zagoria Foundation. ",

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AU - Cooper, Laurence J.N.

AU - Al-Kadhimi, Zaid

AU - DiGiusto, David

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AU - Colcher, David

AU - Raubitschek, Andrew

AU - Forman, Steve J.

AU - Jensen, Michael C.

N1 - Funding Information: Some of this information was presented at the 2003 2nd Annual Rebecca Miriam Guzner Memorial Symposium held at the City of Hope in Duarte California and this review is dedicated to the memory of Rebecca who succumbed to neuroblastoma in July 2000 at the age of 4. Support for the development and clinical application of CD19-specific T cells has been obtained from CA30206, CA33572, The Altschul Foundation, The Abe and Estelle Sanders Foundations, The Amy Phillips Charitable Foundation, The Leukemia and Lymphoma Society, Pediatric Cancer Research Foundation, The Sidney Kimmel Foundation for Cancer Research, The Zagoria Foundation.

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N2 - 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.

AB - 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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Development and application of CD19-specific T cells for adoptive immunotherapy of B cell malignancies

Abstract

Keywords

ASJC Scopus subject areas

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