Nobel Prize in Medicine 2018: How the cancer immunotherapy research can save millions of lives
Another advantage of immunotherapy is its fewer side-effects as compared to other treatment avenues at hand.
Human body is intriguing.
While on one hand it has an active immune system that fights enemies, such as bacterias or viruses, on the other hand, if rheumatoid arthritis happens, then the same immune system goes berserk and turns against its own people (fellow tissues of the joints).
Cancer cells are no less smart as they train immune cells, not to recognise cancer as abnormal. To simply put the application of cancer immunotherapy, the researchers help the cells of immune system to recognise the enemy in cancer cells.
This year’s Nobel Prize for Physiology or Medicine will be shared by James P Allison, 70, of the MD Anderson Cancer Center, University of Texas, USA, and Tasuku Honjo, 76, of the Kyoto University School of Medicine, Japan.
The research work for which they have been awarded was actualised in the 1990s when Prof Allison worked with his teams at the University of California and Memorial Sloan Kettering Cancer Center, New York.
Cancer treatment routinely involves one or combination of surgery, chemotherapy or radiation therapy. A relatively new set of therapy has evolved in the recent years with relevant molecules making it through clinical trials. This immunotherapy, as the Nobel Committee mentions, is through the efforts of the Nobel Laureates who have established it as “new principle for cancer therapy’’.
To be able to recognise and attack cancer cells, T-cells — a subset of immune cells — needs to be activated. Cancer cells escape and go unnoticed by turning off an ‘immune checkpoint’ in T-cells by blocking a receptor (PD-1) on its surface.
How do they do it?
The cancer cells, on their surface, have the ligand of PD-1 called PD-L1. In simple terms, the PD-1 and PD-L1 deactivate the T-cell by fitting in each other as lock and key.
Herein, a checkpoint inhibitor can free the T-cells from the clutches of cancerous cells and attack it as non-self.
In order to be able to activate the T-cell or ‘turn on’, either a PD-1 inhibitor or another molecule (Antibody) that can block PD-L1 have to be administered as potential therapeutics.
Honjo’s work led to the discovery of PD-1 and its role in T-cell function, way back in 1992. This has led to the development and approval of Nivolumab, a PD-1 inhibitor for melanoma (skin cancer) in 2015.
Other approved PD-L1 inhibitors are Avelumab, Atezolizumab.
Allison’s work, on the other hand, was also based on another T-cell expressed molecule-CTLA-4, which acts as a break.
Using CTLA-4 inhibitors in mice models of tumor led to release the break and further killing of cancer cells by the activated T-cell; curing the mice of cancer in the winters of 1994. The enthusiastic researchers repeated the experiment post-Christmas to see reproducibility in outcomes.
Despite lack of interest by the Pharma companies initially, successful treatment of melanoma by Ipilumumab, a highly aggressive form of cancer, in a clinical study, was approved by US Food and Drug Administration (FDA).
Immunotherapy-based checkpoint inhibitors have shown promising results in the treatment of lung cancer, kidney cancer and lymphoma, besides melanoma.
Though cancer immunotherapy is in its nascent stages of clinical application, it is widely recognised and welcomed as a new therapeutic modality.
Another advantage of immunotherapy is its fewer side-effects as compared to other treatment avenues at hand.
The human body has an amazing immune system, which just needs to be given a little nudge to recognise the enemies.
In this case, the viciously growing cancerous mass.
In India, though it would take longer to incorporate immune checkpoint inhibitors in routine usage, owing to cost factor, the promising results of the immunotherapy have paved way for complete cure in some forms of cancer.
This surely ignites hopes for millions suffering from the Emperor of all maladies.