Antibodies for Inflammatory Disease
Their inherent specificity makes antibodies attractive immunotherapeutic agents. Definition of appropriate therapeutic strategies requires parallel identification of potential target molecules and the immunotherapeutic mechanisms to be recruited by antibo
- PDF / 245,225 Bytes
- 16 Pages / 418.32 x 664.56 pts Page_size
- 18 Downloads / 200 Views
99
8 Antibodies for Inflammatory Disease Effector Cells Richard Smith 1. Introduction Their inherent specificity makes antibodies attractive immunotherapeutic agents. Definition of appropriate therapeutic strategies requires parallel identification of potential target molecules and the immunotherapeutic mechanisms to be recruited by antibodies targeting these molecules. Regardless of the target antigen, antibodies may modify immune responses by: 1. 2. 3. 4.
Killing target cells (cytotoxic or depleting antibodies); Blocking molecular interactions; Modulating target molecules from the surface of cells; or Modifying cell function as a consequence of signal transduction by ligated molecules.
In addition to their inherent specificity, the ability to modify antibodyconstant regions in order to selectively recruit these mechanisms of action greatly increases the appeal of antibodies as therapeutic agents. Importantly, these strategies may be recruited to passively suppress or to actively modulate immune responses. Finally, the ability to modify antibody-constant regions in order to minimize antiglobulin responses facilitates the use of these molecules as therapeutic agents. The development of antibodies capable of modifying inflammatory autoimmune disease processes illustrates many of these principles. The ideal scenario for development of a therapeutic monoclonal antibody (mAb) would be to focus on a disease or diseases in which the pathogenic mechanisms are known, develop an effective therapeutic strategy in an animal From: Methods in Molecular Medicine, Vol. 40: Diagnostic and Therapeutic Antibodies Edited by: A. J. T. George and C. E. Urch © Humana Press Inc., Totowa, NJ
99
100
Smith
model in which the same mechanisms are acting, and then develop a molecule for use in humans that recruited the same mechanisms. Immunopathogenic mechanisms are poorly defined in many inflammatory autoimmune diseases, making selection of appropriate animal models difficult. However, data from human disease supports the suggestion that organ-specific autoimmune diseases are T-cell dependent and development of antibodies against the cellular components of the inflammatory autoimmune disease process therefore focuses largely (although not exclusively, vide infra) on T lymphocytes. 2. Immune Responses in Inflammatory Diseases Inflammatory immune responses contribute to the pathogenesis of many human autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, and type 1 diabetes mellitus. They may also contribute to clinical transplant rejection. Selection of target molecules for therapeutic antibodies requires reference to the mechanisms operating in these pathological immune responses. Two cellular components are central to the inflammatory immune response: antigen-specific helper T (Th) lymphocytes acting to focus and coordinate the response, and nonantigen-specific effector cells (predominantly macrophages), which mediate tissue damage (Fig. 1). Therapeutic antibodies may target either of these cell types, the cytokine
Data Loading...
