We propose to mobilize the body's immune system against established cancer. We believe we have discovered key points in the immune network and by combining agents that target those points we can eradicate a larger proportion of cancers.
This project is testing the hypothesis that several different immune pathways can be stimulated in sequence to generate a powerful immune response capable of suppressing established tumour growth.
The proposed studies are designed to address important, fundamental issues of cancer immunology and the work is of immense and immediate benefit to cancer patients. We propose to mobilise the body's own immune system against established cancer.
The particular aim is to develop an effective combined immunotherapy of established cancer based on tumour cell death, dendritic cell activation, and T cell effector function. We believe we have discovered key points in the immune network and now understand that by combining antibodies, glycolipids and cytokines that both kill cancer cells and stimulate these important parts of the immune system in a sequential treatment, we can eradicate a large proportion of established tumours in mice.
We are now testing this therapy in even more rigorous mouse models, and improving it by substituting improved versions of one of the agents at a time, and examining how the therapy works. We have shown that both glycolipids that stimulate sentinel white blood cells called dendritic cells or antibodies that do the same via a molecule called CD1d, can effectively substitute for the classical stimulation afforded by the dendritic cell molecule, CD40.
Antibodies against CD1d are also effective in these combinations and we have established an immune signature that some chemotherapies and radiotherapies prime to partially mediate their effectiveness. These combination therapies offer a range of different approaches to treat established tumours depending upon the tumour microenvironment.