Cancer Institute Seminar Series - Prof Terry Rabbitts

Hosted by Prof David Linch and Dr Marc Mansour

Whole antibodies are challenging for expression inside cells because they are comprised of four chains (two heavy and two light chains) held together by covalent, disulphide bonds.
However, employing just the antigen-binding regions of the heavy or light chains (the CDRs that bind antigen) allows the reduction in their size to single domain intracellular antibody fragments (iDAbs) while exploiting their binding properties within the reducing environment of cells. iDAbs can be used to interfere with protein function in cells by different mechanisms, such as directly interfering with protein-protein interactions, causing enhanced protein turnover or inducing antigendependent cell death. iDAbs are macromolecules (called macrodrugs) that can be introduced into cells as cargoes in lipid nanoparticle vehicles.

Shrinking intracellular antibody fragments even further has been achieved by selecting chemical compounds from libraries by competing the antibody fragment binding sites. Application of intracellular antibody fragments in selecting Antibody-derived (Abd) compounds will be described focussing on the previously considered undruggable mutant RAS protein in cancer. Our general approaches could be applied to any intracellular target protein, within any clinical indication including cancer, neuropathies, infection and auto-immunity.

• Rabbitts Group

A light lunch will be served after the seminar. This seminar has been sponsored in part by the Biomedical Research Centre and Cancer Research UK