Immunotherapy And Cancer: A Plunge In The Dark To Nobel Prize
A novel cancer treatment has just been awarded a Nobel Prize.
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By Holly Leslie
One of the major hallmarks of cancer is the ability of cancer cells to overcome the stress of the host immune system. The ability to strengthen the immune response against cancer continues to be an area of intense research, recently resulting in CAR-T therapy being approved as a treatment for childhood leukaemia. Although many world-class researchers have allowed for immunotherapies to be brought from bench side to clinic, key figures in the field would agree that it was the work of this year’s Nobel Prize in Medicine and Physiology winners, Dr. James Allison (US) and Prof. Tasuku Honjo (Japan), that laid the foundation for such immense advancement in the field.
An approach referred to as ‘immune checkpoint blockade’ continues to be the best-understood mechanism of reprogramming the body’s own immune system to recognise and destroy tumours. Work done by Dr. Allison and Prof. Honjo respectively identified immune cell surface receptors, CTLA-4 and PD-L1, as ones by which cancer cells induce an immunosuppressive effect. By suppressing immune cell function, cancer cells are able to continue to grow, as they are not destroyed. By blocking CTLA-4 and PD-1 with antibodies, as in ipilimumab and pembrolizumab therapy respectively, tumour immune response is maintained; T cells are able to release cytotoxic agents to kill cancer cells preventing proliferation and survival. However, this is one of many cellular events in cancer immunology and the complete understanding of normal immune response to each individual form of cancer remains elusive.
The novel approach of targeting the immune cells rather than the traditional approach of targeting cancer cells has revolutionised the way diseases can be treated. The ability to block multiple pathways involved in evasion of the immune system stress is one that allows synergy between distinct therapies. Furthermore, combination of two (or more) different immunotherapies may overcome the problem of chemotherapeutic resistance.
Despite it now seeming like an obvious concept in the development of cancer therapy, Allison recalled the frustration that he felt when pharmaceutical companies initially doubted the evidence. Jerome Galon from INSERM, Paris, explained the major advantage of such immunotherapies is shown through the observed increase a patient’s lifetime by years, instead of months.
Admittedly, decades of research are still required before the world will fully appreciate the outstanding contribution to medicine provided by Dr. Allison and Prof. Honjo. Immunotherapies are currently very expensive to obtain and not one immunotherapy has shown to be curative of any cancer. It is important to remember that each cancer subtype, of which there are likely to be millions, has the potential to require a distinct immunotherapy. The task is immense, but its full potential is now known by many.