A pharmacologic perspective on newly emerging T-cell manipulation technologies

Authors


Correspondence

Dr Dominic P. Smethurst MA MBChB MRCP MFPM, Adaptimmune Ltd & Immunocore Ltd, 57c Milton Park, Abingdon Oxfordshire OX14 4RX, UK

Tel.: +44 12 3543 8610

Fax: +44 12 3543 8607

E-mail: dominic.smethurst@immunocore.com

Abstract

T cells are a multifaceted family pivotal in the operations of the immune system and many of its associated diseases. The pathway to understanding T cells has been marked by several pharmacological advances including the discoveries of ciclosporin, tacrolimus and the mTOR inhibitors which revolutionized transplant therapy along with providing relief for severe eczema, asthma and other immunological disorders towards the end of the last century. This article will revisit the current understanding and new developments in T cell pharmacology 10 years on from the TeGenero (TGN 1412) debacle and look at more recent successes with ex vivo antigen presenting cell incubation technologies; T cell receptor (TCR) engineering and adoptive T cell therapy both with chimaeric antibodies and also with modified T cell receptors themselves. Features of T cell biology will be explored and processes often highly unique to humans will be used to highlight what many are beginning to see as an exciting new monoclonal (T cell) frontier for drug development.

Ancillary