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

Authors: Brentjens, R. J.; Curran, K. J.
Article Title: Novel cellular therapies for leukemia: CAR-modified T cells targeted to the CD19 antigen
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.
Keywords: adult; child; leukemia; transplantation, homologous; genetics; disease course; review; methodology; t lymphocyte; t-lymphocytes; cytology; biological model; models, biological; recurrence; hematopoietic stem cell transplantation; transplantation; gene transfer; immunology; lymphocyte activation; disease progression; recurrent disease; natural killer cell; adoptive transfer; killer cells, natural; leukocyte; adoptive immunotherapy; immunotherapy, adoptive; cd19 antigen; antigens, cd19; allotransplantation; gene transfer techniques; leukocytes
Journal Title: Hematology-American Society of Hematology Education Program
Volume: 2012
ISSN: 1520-4391
Publisher: American Society of Hematology  
Date Published: 2012-01-01
Start Page: 143
End Page: 151
Language: English
PUBMED: 23233573
PROVIDER: scopus
PMCID: PMC5536093
Notes: --- - "Export Date: 1 August 2013" - "Source: Scopus"
Citation Impact
MSK Authors
  1. Renier J Brentjens
    274 Brentjens
  2. Kevin Joseph Curran
    101 Curran