Immunodrugs: breaking B- but not T-cell tolerance with therapeutic anticytokine vaccines

Abstract

Pathology in most chronic inflammatory diseases is characterized by an imbalance in cytokine expression. Targeting cytokines with monoclonal antibodies has proven to be a highly effective treatment. However, monoclonal antibody therapy has disadvantages such as high production costs, generation of antimonoclonal antibodies and the inconvenience of frequent injections. Therapeutic vaccines have the potential to overcome these limitations. The aim of active vaccination is to induce B-cell responses and obtain autoantibodies capable of neutralizing the interaction of the targeted cytokine with its receptor. In order to achieve this, therapeutic vaccines need to circumvent the potent tolerance mechanisms that exist to prevent immune responses against self-molecules. This article focuses on the tolerance mechanisms of the B- and T-cell compartments and how these may be manipulated to obtain high-affinity autoantibodies without inducing potentially dangerous autoreactive T-cell responses.

KEYWORDS::

• B cell
• cytokine
• immunotherapy
• inflammatory disease
• monoclonal antibody
• T cell
• therapeutic vaccination
• tolerance

Acknowledgements

We would like to thank Gary Jennings and Gunther Spohn for discussion and critical reading of the manuscript.

Financial & competing interests disclosure

The authors are employees of Cytos Biotechnology AG, Switzerland, and are holders of stocks or stock options in the company. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.