Appropriate targets for monoclonal antibodies in the induction of transplantation tolerance

Lechler, Robert I.; Chai, Jian-Guo; Marelli‐Berg, Federica M.; Lombard, Giovanna

doi:10.1098/rstb.2001.0841

Phil. Trans. R. Soc. Lond. B

2001

DOI: 10.1098/rstb.2001.0841

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Appropriate targets for monoclonal antibodies in the induction of transplantation tolerance

Robert I. Lechler

Jian-Guo Chai

Federica M. Marelli‐Berg

et al.

Abstract: There are many routes to exploiting tolerance processes to ensure long-term graft survival. Complete tolerance although attractive as a goal, may not be the most practical in the clinic. Instead simple and low-impact procedures that harness tolerance processes used in conjunction with low doses of immunosuppressive drugs may prove the most reliable and user-friendly of approaches.

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Cited by 4 publications

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A review of Campath in autoimmune disease: Biologic therapy in the gray zone between immunosuppression and immunoablation

Reiff

2005

Hematology

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Campath, the subject of this review, is an example of a broadly targeted biologic agent, approved for patients with B-CLL, which may combine immunosuppressive as well as immunoablative properties. For many years Campath has been in clinical use as an immunosuppressive agent for various autoimmune diseases and as part of the preparative regimes for allogeneic HSCT, successfully preventing graft-versus-host-disease (GVHD). This review summarizes the experience of 24 studies including a total of 323 patients treated with Campath for various autoimmune diseases such as arthritis, MS, vasculitis, autoimmune cytopenias and others. The results demonstrate that Campath is fairly safe and 75% of the patients experienced clinical improvement and 15% of the patients were reported in clinical remission even though improvements were often transient.While other biologic drugs may have to narrow targets, Campath, is able to bridge the gap between immunosuppression and immunoablation and may offer an alternative to human stem cell transplantation avoiding the risks of chemotherapy and radiation.

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A review of Campath in autoimmune disease: Biologic therapy in the gray zone between immunosuppression and immunoablation

Reiff

2005

Hematology

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Thymoglobulin: an immunologic overview

Mueller¹

2003

Current Opinion in Organ Transplantation

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Immune privilege induced by regulatory T cells in transplantation tolerance

Cobbold

Adams

Graça

et al. 2006

Immunological Reviews

125

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Immune privilege was originally believed to be associated with particular organs, such as the testes, brain, the anterior chamber of the eye, and the placenta, which need to be protected from any excessive inflammatory activity. It is now becoming clear, however, that immune privilege can be acquired locally in many different tissues in response to inflammation, but particularly due to the action of regulatory T cells (Tregs) induced by the deliberate therapeutic manipulation of the immune system toward tolerance. In this review, we consider the interplay between Tregs, dendritic cells, and the graft itself and the resulting local protective mechanisms that are coordinated to maintain the tolerant state. We discuss how both anti-inflammatory cytokines and negative costimulatory interactions can elicit a number of interrelated mechanisms to regulate both T-cell and antigen-presenting cell activity, for example, by catabolism of the amino acids tryptophan and arginine and the induction of hemoxygenase and carbon monoxide. The induction of local immune privilege has implications for the design of therapeutic regimens and the monitoring of the tolerant status of patients being weaned off immunosuppression.

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Appropriate targets for monoclonal antibodies in the induction of transplantation tolerance

Cited by 4 publications

References 36 publications

A review of Campath in autoimmune disease: Biologic therapy in the gray zone between immunosuppression and immunoablation

A review of Campath in autoimmune disease: Biologic therapy in the gray zone between immunosuppression and immunoablation

Thymoglobulin: an immunologic overview

Immune privilege induced by regulatory T cells in transplantation tolerance

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