Therapeutic antibody discovery could lead to new cancer drug development
A group of Cancer Research UK-supported researchers at the University of Leicester have played a major role in the development and validation of an innovative approach to the discovery of potent therapeutic antibodies, which could help to lay the foundations for a new cancer drug.
Professor Mark Carr’s structural biology group at the University of Leicester, working with teams at Cancer Research UK, the AstraZeneca Antibody Alliance Laboratory in Cambridge, and Oxford University, have developed a potent candidate therapeutic antibody against a novel enzyme target Arginase 2, called C0021158.
Arginase 2 (ARG2) is implicated in major human diseases, including cancer. It targets and destroys L-arginine, an amino acid crucial for immune cells to fight infections and diseases. While ARG2 is necessary to control arginine levels in the body, it is over produced in individuals with various types of cancer.
Professor Mark Carr, Structural Biologist at the University of Leicester, said: “The outstanding success of the ARG2 therapeutic antibody project is an example of the substantial benefits to be gained in drug discovery from harnessing the complementary scientific expertise and knowledge available in the pharmaceutical industry, biomedical charity and University sectors of the UK life sciences community. The outcomes from this project point to a successful future for the joint Cancer Research-AstraZeneca Antibody Alliance Laboratory and my structural biology group look forward to further successful collaborations."
The surplus ARG2 significantly reduces L-arginine levels around tumours, hindering the immune cells and creating a local environment that allows tumours to grow unchecked. ARG2 is therefore an attractive target for inhibitory therapeutic antibodies that could help restore immune function against certain types of cancer, such as pancreatic ductal adenocarcinoma, bowel cancer and acute myeloid leukaemia.
The researchers expect that C0021158 will pave the way for the discovery of a new generation of antibodies, with treatment applications in cancer and beyond. Protein crystallography at Leicester provided key insights into the mechanism of the antibody.
Study author Dr Maria Groves, from Cancer Research UK – AstraZeneca Antibody Alliance Laboratory, said: “It takes a lot of time and resources to bring a new therapeutic antibody to the clinic, so we need them to be the best they can be. This first success gives me confidence that our unbiased libraries will produce stronger, more efficient antibodies, which previously could not be found.There’s still a long way to go with our ARG2 antibody, and we are now hoping to partner with a company to help develop the antibody and progress it into the clinic for oncology and non-oncology indications. For oncology, we hope that in combination with chemotherapy or immunotherapy, it may help target tumours that have been hiding from the immune system.”