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Costimulation blockade: towards clinical application.

Publication ,  Journal Article
Weaver, TA; Charafeddine, AH; Kirk, AD
Published in: Front Biosci
January 1, 2008

Organ transplantation is an increasingly successful therapy for many forms of organ failure, but its success depends upon drug therapies to prevent immunologic destruction of the transplanted organ also known as rejection. Most therapies designed to prevent rejection alter the immune system in a rather broad, antigen independent way, and thus alter protective immunity as well as immune responses directed against the transplanted organ. Over the past 3 decades, however, it has been realized that a class of surface molecules known as costimulatory receptors are required to generate a fully productive immune response, and that blockade of these receptors during allo-antigen recognition can be used to influence the immune system's future response to that particular allo-antigen. Costimulation blockade has thus been developed as a specific field of interest towards achieving improved antigen specific control over transplant rejection while minimizing broad attenuation of protective immunity seen with conventional immunosuppressives. This field has grown rapidly in the past decade and is now poised to become a valuable therapeutic option for transplant clinicians. This review will outline the basic premise of costimulation biology, review the seminal experimental basis for its use in preventing organ rejection, and discuss the relevant data derived from its initial use in clinical transplant trials. Specific attention will be focused on two major costimulatory pathways, the CD28/CD80-CD86 and the CD40-CD154 pathways, and the clinically applicable data supporting their validity as therapeutic targets. Newly discovered costimulatory pathways will also be discussed as potential therapeutic targets for future clinical drugs.

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Published In

Front Biosci

DOI

ISSN

1093-9946

Publication Date

January 1, 2008

Volume

13

Start / End Page

2120 / 2139

Location

United States

Related Subject Headings

  • Transplantation Immunology
  • T-Lymphocytes
  • Recombinant Fusion Proteins
  • Organ Transplantation
  • Neoplasms
  • Models, Biological
  • Ligands
  • Immunosuppressive Agents
  • Humans
  • Graft Rejection
 

Citation

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Weaver, T. A., Charafeddine, A. H., & Kirk, A. D. (2008). Costimulation blockade: towards clinical application. Front Biosci, 13, 2120–2139. https://doi.org/10.2741/2829
Weaver, Timothy A., Ali H. Charafeddine, and Allan D. Kirk. “Costimulation blockade: towards clinical application.Front Biosci 13 (January 1, 2008): 2120–39. https://doi.org/10.2741/2829.
Weaver TA, Charafeddine AH, Kirk AD. Costimulation blockade: towards clinical application. Front Biosci. 2008 Jan 1;13:2120–39.
Weaver, Timothy A., et al. “Costimulation blockade: towards clinical application.Front Biosci, vol. 13, Jan. 2008, pp. 2120–39. Pubmed, doi:10.2741/2829.
Weaver TA, Charafeddine AH, Kirk AD. Costimulation blockade: towards clinical application. Front Biosci. 2008 Jan 1;13:2120–2139.

Published In

Front Biosci

DOI

ISSN

1093-9946

Publication Date

January 1, 2008

Volume

13

Start / End Page

2120 / 2139

Location

United States

Related Subject Headings

  • Transplantation Immunology
  • T-Lymphocytes
  • Recombinant Fusion Proteins
  • Organ Transplantation
  • Neoplasms
  • Models, Biological
  • Ligands
  • Immunosuppressive Agents
  • Humans
  • Graft Rejection