Monoclonal antibodies (mAbs) are a type of biological therapy that work by targeting specific molecules, known as antigens, on cancer cells. Cancer cells express complex sugars on these antigens which are vital for their survival.
The team has shown that mAbs binding to these sugars can cause cancer cell death. They propose to make a killing mAb against a novel tumour specific sugar, the Forssman sugar, with potent anti-cancer activity. This sugar is not normally present in humans but has been found in bowel cancer. It is difficult to purify or synthesize and does not stimulate strong antibody responses. The antibodies made to date are not Forssman specific.
In collaboration with Professor Yamamato (Barcelona), the team has engineered a tumour cell line to only express the Forssman sugar. They will use this cell line with their technology to generate a new human mAb. This mAb will then be evaluated in the laboratory for its ability to kill cancer but not normal cells.
The project is being led by Lindy Durrant, Professor of Cancer Immunotherapy in the Department of Oncology at Nottingham University.
Why develop monoclonal antibodies for bowel cancer treatment?
Colorectal cancer remains one of the biggest cancer killers, with survival rates for advanced bowel cancer being very poor, with only around 6 in 100 people surviving post 5 years. Biological therapies such as Avastin, Vectibix, and Zaltrap, are relatively new and are showing promise in bowel cancer treatment.
Cetuximab (Erbitux) is licensed in the UK for advanced bowel cancer and can help some people live longer when administered with standard chemotherapy (5FU (fluorouracil), oxaliplatin, or irinotecan). However, although some bowel cancer cells have receptors for epidermal growth factor (EGF) which Cetuximab can block, recent research has revealed that between 3 and 4 out of every 10 advanced bowel cancers (35 to 40%) have a mutation in the k-ras gene against which Cetuximab is ineffective.