Adoptive immunotherapy for B-cell malignancies with autologous chimeric antigen receptor modified tumor targeted T cells Journal Article


Authors: Park, J. H.; Brentjens, R. J.
Article Title: Adoptive immunotherapy for B-cell malignancies with autologous chimeric antigen receptor modified tumor targeted T cells
Abstract: Chemotherapy-resistant B-cell hematologic malignancies may be cured with allogeneic hematopoietic stem cell transplantation (HSCT), demonstrating the potential susceptibility of these tumors to donor T-cell mediated immune responses. However, high rates of transplant-related morbidity and mortality limit this approach. For this reason, there is an urgent need for less-toxic forms of immune-based cellular therapy to treat these malignancies. Adoptive transfer of autologous T cells genetically modified to express chimeric antigen receptors (CARs) targeted to specific tumor-associated antigens represents an attractive means of overcoming the limitations of conventional HSCT. To this end, investigators have generated CARs targeted to various antigens expressed by B-cell malignancies, optimized the design of these CARs to enhance receptor mediated T cell signaling, and demonstrated significant anti-tumor efficacy of the resulting CAR modified T cells both in vitro and in vivo mouse tumor models. These encouraging preclinical data have justified the translation of this approach to the clinical setting with currently 12 open clinical trials and one completed clinical trial treating various B-cell malignancies utilizing CAR modified T cells targeted to either the CD19 or CD20 B-cell specific antigens.
Keywords: clinical trial; clinical trials as topic; methodology; t lymphocyte; t-lymphocytes; animal; animals; b cell lymphoma; lymphoma, b-cell; immunology; hybrid protein; recombinant fusion proteins; immunomodulation; adoptive immunotherapy; immunotherapy, adoptive; cd19 antigen; lymphocyte antigen receptor; antigens, cd19; receptors, antigen
Journal Title: Discovery Medicine
Volume: 9
Issue: 47
ISSN: 1539-6509
Publisher: Solariz, Inc.  
Date Published: 2010-04-01
Start Page: 277
End Page: 288
Language: English
PUBMED: 20423671
PROVIDER: scopus
PMCID: PMC4697441
DOI/URL:
Notes: --- - "Export Date: 20 April 2011" - "Source: Scopus"
Citation Impact
MSK Authors
  1. Renier J Brentjens
    267 Brentjens
  2. Jae Hong Park
    221 Park