Expert opinion: Super T cells in cancer therapy: taking the brakes off the immune system
The immune system has long been known to have an important role in stopping cancer, and immune suppression is a well-established risk for cancer formation.
Numerous attempts to harness the immune system in cancer therapy have been made over the last 30 years, starting with the use of mashed-up, heat inactivated tumours as a vaccine and subsequently more refined methods using specific cancer-associated proteins. However, these approaches have generally given very disappointing results in clinical trials. More recently a radically different and far more effective approach has been taken, which involves removing the naturally occurring inhibitors or “breaks” acting on the immune system.
This works because many tumours produce proteins that block immune function. One of the most important of these is the PD-1 ligand, which binds to the PD-1 protein on the surface of T-cells, one of the most important immune cell types that can actually invade tumours and selectively kill cancer cells. Tumours that make PD-1 ligand are able to switch T cells to an inactive state, blocking the immune response and allowing unrestricted tumour growth.
One approach to overcome this is the use of antibodies that bind to PD-1 and prevent this interaction between cancer cells and T-cells. Anti-PD1 antibodies have proved very effective in clinical trials, most notably for advanced melanoma, and have achieved long term disease control or even a cure in some patients. However, this approach comes with a high cost, both financially and in terms of side effects; the anti-PD1 antibody activates almost all of the T cells in the body, not just those in the tumour, and this can lead to severe autoimmune symptoms when the T-cells attack healthy tissue.
Now a team at University College London (UCL) have taken a step towards overcoming this difficulty by taking T-cells from a tumour and genetically changing them so they no longer make PD-1 protein. When put back in the patient, these cells should in theory only attack tumor cells, thus preventing side effects. These “super T cells” showed significant promise in mice, blocking tumour growth and prolonging survival. However, there is still a lot more to do before this can be used in humans, and as always with these elegant but very complex genetic interventions, the cost per patient would be expected to be prohibitive. A simpler, drug based approach to achieving the same outcome is still needed, but this valuable work from UCL once again demonstrates the enormous potential of immunotherapy in cancer treatment.
, Professor of Molecular Oncology reacting to BBC News article on Gene editing 'boosts' cancer-killing cells.