Document Detail


Development of adoptive cell therapy for cancer: a clinical perspective.
MedLine Citation:
PMID:  20408760     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Adoptive cellular therapy provides the promise of a potentially powerful general treatment for cancer. Although this is a complex and challenging field, there have been major advances in basic and translational research resulting in clinical trial activity that is now beginning to confirm this promise. However, these trials are also identifying new challenges and this review focuses on these clinical issues. For tumors such as melanoma, in which tumor-specific T cells can be readily identified and isolated, the adoptive transfer of "tumor-infiltrating lymphocytes" (TILs) already appears to offer significant patient benefit and this approach now warrants further development. Genetically engineered T cells offer a means to endow peripheral blood T cells with antitumor activity and in principle these techniques could allow the treatment of a wide range of cancers. Genetic engineering also offers the means to endow T cells with new properties and enhanced functions. There have been clear proof-of-principle trials showing responses with T cell receptor (TCR)-engineered T cells and this can be built on with further development. By contrast, other trials have produced significant toxicity related to expression of target antigen on normal tissue, particularly with enhanced receptors. The challenge ahead lies in understanding how to achieve the balance between targeted antitumor immune responses while avoiding toxicity associated with on-target destruction of antigen-expressing normal tissues. Cellular therapy of cancer will need continued preclinical evaluation as well as carefully designed clinical trials addressing the various issues. For these challenges to be fully assessed, and for progression to a widely used, effective and safe therapy, development as cooperative groups is an appropriate way forward.
Authors:
Robert E Hawkins; David E Gilham; Reno Debets; Zelig Eshhar; Naomi Taylor; Hinrich Abken; Ton N Schumacher; ATTACK Consortium
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Human gene therapy     Volume:  21     ISSN:  1557-7422     ISO Abbreviation:  Hum. Gene Ther.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-06-10     Completed Date:  2010-09-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9008950     Medline TA:  Hum Gene Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  665-72     Citation Subset:  IM    
Affiliation:
Cellular Therapy Group, School of Cancer and Enabling Sciences, The Paterson Institute of Cancer Research, The University of Manchester, Wilmslow Road, Manchester, UK. Rhawkins@picr.man.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Adoptive Transfer
Cancer Vaccines
Clinical Trials as Topic
Genetic Engineering
Humans
Lymphocytes, Tumor-Infiltrating / immunology
Neoplasms / immunology,  therapy*
Nervous System Neoplasms
Receptors, Antigen, T-Cell / genetics,  immunology
T-Lymphocytes / immunology
Tissue Therapy
Translational Research
Chemical
Reg. No./Substance:
0/Cancer Vaccines; 0/Receptors, Antigen, T-Cell

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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