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PMID: 23233573 Published · ppublish English Journal Article Review

Novel cellular therapies for leukemia: CAR-modified T cells targeted to the CD19 antigen.

Hematology. American Society of Hematology. Education Program ·Vol. 2012 ·2012-00-00 ·Pages 143-51

Brentjens RJ, Curran KJ

Abstract

The ability of immune-competent donor T cells to mediate a beneficial graft-versus-leukemia (GVL) effect was first identified in the setting of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematologic malignancies. Unfortunately, with the exception of chronic myelogenous leukemia and EBV-induced lymphoproliferative disease, allo-HSCT GVL lacks the potency to significantly affect disease progression or recurrence in most other hematologic malignancies. The inadequacy of a GVL effect using past approaches is particularly evident in patients with lymphoid malignancies. However, with the advent of improved gene transfer technology, genetically modified tumor-specific immune effectors have extended cellular immunotherapy to lymphoid malignancies. One promising strategy entails the introduction of genes encoding artificial receptors called chimeric antigen receptors (CARs), which redirect the specificity and function of immune effectors. CAR-modified T cells targeted to the B cell-specific CD19 antigen have demonstrated promising results in multiple early clinical trials, supporting further investigation in patients with B-cell cancers. However, disparities in clinical trial design and CAR structure have complicated the discovery of the optimal application of this technology. Recent preclinical studies support additional genetic modifications of CAR-modified T cells to achieve optimal clinical efficacy using this novel adoptive cellular therapy.

MeSH Terms
Adoptive Transfer Adult Antigens, CD19/genetics,immunology Child Disease Progression Gene Transfer Techniques Hematopoietic Stem Cell Transplantation/methods Humans Immunotherapy, Adoptive/methods Killer Cells, Natural/cytology Leukemia/immunology,therapy Leukocytes/cytology Lymphocyte Activation/immunology Models, Biological Recurrence T-Lymphocytes/immunology,transplantation Transplantation, Homologous
Chemicals
Antigens, CD19
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Brentjens Renier J
Memorial Sloan-Kettering Cancer Center, New York, New York, NY 10065, USA. brentjer@mskcc.org
Curran Kevin J
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Article Info
Journal
Hematology. American Society of Hematology. Education Program
Abbr.
Hematology Am Soc Hematol Educ Program
ISSN
1520-4383
DOI
10.1182/asheducation-2012.1.143
Email
brentjer@mskcc.org
Published
2012-00-00
Pages
143-51
Language
English
Region
United States
NLM ID
100890099
PMCID
PMC5536093
Subset
IM
Grants
NCI NIH HHS · P30 CA008748 · United States
External Links
PubMed source DOI: 10.1182/asheducation-2012.1.143 PMC Full Text View journal details
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