Katherine Vallis, Professor of Experimental Radiotherapeutics at the University of Oxford’s Department of Oncology, has been awarded new funding from the MRC for her project concerning the use of cell-permeant antibodies for the treatment of acute leukaemia.
The MRC Developmental Pathway Gap Fund aims to support projects that will fill in critical evidence gaps to inform the development of novel therapeutics, devices, or diagnostic tools. The funding will allow Prof. Vallis and her team to generate in vivo data on the use of cell-penetrating peptides (CPPs) for cancer applications, a crucial step towards clinical translation.
The challenge of ‘undruggable’ proteins
It has been estimated that 85% of human proteins are ‘undruggable’ due to their location, structure, or mechanism of action. While great strides have been made in the development of novel small molecules and immunotherapeutic agents for cancer treatment, many putative targets remain unexploited. Intracellular proteins that lack binding pockets or have large protein-protein interaction interfaces are often considered undruggable, as small molecules can’t bind to them. Targeting these proteins is a key challenge in cancer research that requires the development of innovative technologies.
Antibodies are well suited to meet this need, as they are highly specific and don’t require a binding pocket to attach to their target. However, their large size prevents them from entering cells. Designing methods for the intracellular delivery of antibodies is of great interest to researchers in cancer medicine, but lack of efficacy and toxicity concerns associated with existing delivery vehicles has hindered progress.