A new method to enhance cancer treatment
Researchers at the University of Louvain de Duve Institute have successfully managed to defuse a molecule in the body which blocks the ability of the immune system to attack cancer. By doing so, this immunotherapy is able to enhance another immunotherapy which is ineffective in certain patients and allows tumour shrinkage.
The immune system is vital in the protection and fight against infections and cancers. It is closely regulated by T cells (Tregs) which ensure the system is partially supressed when there is no imminent threat of cancer or chronic infections to avoid autoimmune responses. If traces of disease are picked up on by surveying cells, the immune system is triggered and acts to destroy the pathogen or faulty cell.
The scientists recognised that a large proportion of cancer patients do not respond to conventional immunotherapy methods due to resistance to T-cell-mediated anti-tumour immunity, meaning their Treg cells were unable to release immune suppression and allow for immune cell-mediated attack on cancer cells. This defect in has also been recently linked to disease hyperprogression, suggesting that patients with supressed immune systems due to Treg dysfunction have more aggressive tumours.
Researchers have attempted to harness the immune system for the treatment of cancer since the late 19th Century. William B. Coley, the Father of Immunotherapy, first began the development of immuno-oncology by injecting bacteria into tumours after noticing a large proportion of cancer patients entered remission following an infection. This was because the immune system began to attack the bacteria in the tumours, whilst simultaneously destroying cancer cells.
Scientists have optimised this method to prevent the risks associated with deliberately infecting patients with pathogens. Current methods include vaccines, checkpoint inhibitors and Adoptive T-cell therapy.
Vaccines are designed to either prevent the emergence of cancer, or to introduce monoclonal antibodies against specific receptors on cancer cells and target them for destruction by cytotoxic T cells. Checkpoint inhibitors target the process of deactivating T cells, thereby ensuring the immune system is free to attack cancer cells. This immunotherapy encourages the patients’ own T cells to attack cancer cells, whereas other methods including Adoptive T-cell therapy, involve the transfusion of mature T-cells into a patient which are immediately able to attack cancer cells.
The new immunotherapy method developed by researchers at the University of Louvain de Duve is a combination of monoclonal antibody therapy and checkpoint inhibitors which target Tregs and block their function. By doing so, the immune system de-supressed and is free to target cancer cells. The monoclonal antibody was also found to promote the function of anti-tumour T cells in mice, thereby dually strengthening the action of the immune system. There is real prospect for this immunotherapy in the clinic as it was also found to enhance the effects of another anti-PD1-therapy, to which a large proportion of cancer patients are resistant to.
Grégoire de Streel, Charlotte Bertrand, Nicolas Chalon, Stéphanie Liénart, Orian Bricard, Sara Lecomte, Julien Devreux, Mélanie Gaignage, Gitte De Boeck, Lore Mariën, Inge Van De Walle, Bas van der Woning, Michael Saunders, Hans de Haard, Elien Vermeersch, Wim Maes, Hans Deckmyn, Pierre G. Coulie, Nicolas van Baren, Sophie Lucas. Selective inhibition of TGF-β1 produced by GARP-expressing Tregs overcomes resistance to PD-1/PD-L1 blockade in cancer. Nature Communications, 2020; 11 (1) DOI: 10.1038/s41467-020-17811-3