New Therapeutic Antibodies

Project researcher: Dr Chris Paluch, Academic Foundation doctor

During the academic foundation programme, Chris worked in Professor Richard Cornall and Professor Simon Davis' labs on a project titled 'New Therapeutic Antibodies: Inhibitory Superagonists'. He will continue this project as a DPhil student over the next 3 years.

Adverse lymphocyte activation and growth are the cause of autoimmune disease, hypersensitivity, lymphoid cancer and transplant rejection. Lymphocyte fate is decided not just by antigen-binding but also by activating or inhibitory co-receptors.

Understanding these processes has led to the development of inhibitory antibodies that block the interaction of the activating receptors with their ligands. The parallel strategy of developing agonistic antibodies that directly activate inhibitory pathways in lymphocytes could be a major therapeutic advance.

Work carried out previously in the Cornall / Davis labs on the molecule PD-1 suggests that antibodies can be developed that act as superagonists to inhibitory T cell receptors, and that these can have inhibitory effects on immune cells. This has paved the way to developing a new genre of therapeutic antibody.

The project seeks to establish that a general class of potentially therapeutic antibodies of this type exists by generating superagonistic antibodies to 3 other potent inhibitory T cell receptors – BTLA, CD200R and TIGIT. The project will then investigate their potential for immune modulation.

August 2015