How To Improve Antibody Targeting In Cancer Treatment?

Scientists have gained new insight on how the immune system can be better used to find and kill cancer cells. They showed that antibodies which are designed to target the molecule OX40, give a more active immune response when they bind closer to the cell membrane and can be modified to attack cancer in different ways.

The research conducted by Professor Mark Cragg and Dr Jane Willoughby from the Antibody and Vaccine Group at the University of Southampton's Centre for Cancer Immunology along with BioInvent International is published in the Journal for ImmunoTherapy of Cancer.

‘In cancer treatment, anti-OX40 antibodies target the mIgG2a isotype and delete cells called Treg cells to kill the cancer cells.’

During an immune response, OX40 is a 'co-receptor' that helps to stimulate the production of helper and killer T-cells. The cancer cells avoid the detection by suppressing immune responses to stop functional tumor specific T-cells from being produced.

In the study, the team found that switching the antibody's isotype (the part of the antibody that engages with cells of the immune system) could change the way the antibody worked. By using the mIgG2a isotype, the antibody could delete cells called Treg cells which are suppressive in the immune system. In the presence of mIgG1 isotype, the antibody could stimulate killer T-cells to increase and therefore kill more cancer cells.

Professor Cragg said, "Clinical trials with anti-OX40 antibodies have shown that the body can tolerate these drugs but unfortunately have also shown disappointing clinical responses. We need to understand why this is. This new data shows us that when there is a cancer with lots of Tregs we could use the equivalent of the m2IgGa isotype and in patients where we feel we need better cytotoxic T cells we could use the equivalent of a mIgG1 isotype to boost the immune response. This information is important for developing the next generation of OX40 antibodies that we hope will be more effective in treating patients with cancer."

Source: Medindia