Avidex Technology Yields Novel Immunotherapeutic Protein Platform
Tuesday March 1, 4:00 am ET
Key Data on Phage Display Engineering of mTCRs Published in Nature Biotechnology
OXFORD, England, March 1 /PRNewswire/ -- Avidex today announces publication of data that for the first time demonstrates that soluble, high affinity, human monoclonal T cell receptors (mTCRs) can be selected using phage display technology. This is a breakthrough that paves the way for the development of new immunotherapeutics based on the T cell immune response which has so far been largely unexplored. Details of the scientific achievement are published today in the journal Nature Biotechnology, in paper entitled 'Directed evolution of human T cell receptors with picomolar affinities by phage display'.
Mr James Noble, CEO of Avidex commented: "This is an amazing achievement for a small biotech company given the enormous technical hurdles. Avidex can routinely produce high affinity mTCRs and is developing a new protein therapeutic platform based on phage display. Companies like Cambridge Antibody Technology, Dyax and Morphosys all started out with such platforms but on the antibody side. Avidex is the only company worldwide that produces naturally folded, soluble and now high affinity human mTCRs using phage display. This opens up significant new avenues for immunotherapy for the treatment of major diseases such as autoimmune diseases, viral diseases and cancer."
T cell receptors, like antibodies, have long been recognised as attractive as possible therapeutics as they are used by the immune system to recognise abnormal body cells, for example cancer cells or cells infected by virus. There are now more than 12 monoclonal antibody products registered as drugs and over 200 are in clinical trials. Until now, however, attempts to isolate and produce soluble, stable and high affinity TCRs for the use in antibody-like products have not been successful and this has hampered the development of TCRs for therapeutic uses.
The T cell mediated immune response is triggered by the highly specific interaction between TCRs and the 'peptide antigen', a structure at the surface of the antigen-presenting cell (APC) that combines the antigen and the HLA complex (human leukocyte antigen). Peptide antigens play a key role in the onset of many diseases and represent the most comprehensive range of potential therapeutic targets including intracellular, cell-surface-expressed or secreted targets.
Dr Bent Jakobsen, Chief Scientific Officer of Avidex, said "The affinities (KDs) of natural TCRs for antigens are extremely low. The binding half-lives of natural TCRs, in the range of only a few seconds, are insufficient to enable stable cell-surface adhesion of a soluble TCR, as would be required for therapeutic use. Our recent breakthrough has produced monoclonal human TCRs with picomolar affinities, representing a million-fold improvement over the affinity of natural TCRs. Avidex's technology can be applied to any TCR and can be used to screen phage libraries of 10 to the tenth power variants. These extremely high-affinity TCRs exhibit reduced cross-reactivity and are exquisitely specific for the antigen they recognise."
About Avidex
Avidex is a biotechnology company focused on the development of small molecule modulators of T cell function and protein therapeutics based on T cell receptors.
Avidex's breakthrough monoclonal T cell receptor (mTCR) technology enables the production of fully human, soluble T cell receptors. Avidex uses its high affinity T cell receptors to target T cell antigens presented on the surface of cells as HLA-peptides. Avidex selects and affinity matures mTCRs using its proprietary phage display system and can select an mTCR against any T cell antigen or HLA-peptide combination. T cell antigens are not generally available for antibody based approaches, making Avidex's mTCRs unique.
Avidex mTCRs have multiple applications including validation of T cell antigens for therapeutic approaches and diagnostic use. Avidex is developing therapeutic mTCRs which target T cell antigens for cancer and autoimmune disease. mTCRs can deliver immunological effector molecules to destroy cancer cells, and block activation of T cells by delivery of immunoinhibitory cytokines to proprietary autoimmune disease targets.
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