Tumour-Specific Delivery of MCL1 Inhibitors Using Novel Peroxynitrite Cleavable Antibody-Drug Conjugates

The startling statistic that 1 in 2 people will develop some form of cancer during their lifetime means there is an urgent need to develop new precision cancer medicines. However, many cancer drugs adversely affect healthy cells, causing serious side effects and preventing these drugs from progressing clinically.

MCL1 is an important cancer drug target, suppressing programmed cell death (apoptosis) in many malignancies. However, clinical trials with specific MCL1 inhibitors have been halted due to cardiotoxicity.

Antibody-mediated delivery of MCL1 inhibitors specifically to malignant B-cells using antibody drug conjugates (ADCs) could harness the high therapeutic potential of MCL1 inhibitors, whilst removing toxicities.

This studentship will involve chemical synthesis and biological evaluation of novel ADCs for the targeted delivery of potent MCL1 inhibitors to malignant B-cells.

You will join a highly interdisciplinary chemical/biology project, involving the synthesis of novel MCL1 ADCs using a novel linker, cleavable only in malignant B-cells with high ROS levels. You will have an industrial placement in Cambridge with Isogenica, who will provide B-cell specific VHH antibodies.

The studentship will provide a unique portfolio of chemical and biological skills necessary for a career in life sciences in academia/biotech or drug discovery in the pharmaceutical industry.