Immune Checkpoint Inhibitors


Japanese original unique chemotherapy


Chemotherapy will be drastically changed by miracle drugs that activate the human's immune system. 


During an immune response, the immune system attacks potentially harmful substances.  The immune system also stops attacking them.  This immune mechanism controls the immune response and prevents healthy tissues from being damaged.





T cells are immune cells that can kill cancer cells.  The T cell has receptors to which other cells can attach and activate or inactivate the T cell.


Some cancer cells can bind to the receptors on activated T cells and inactivate them.  Immune checkpoint inhibitors are drugs that prevent cancer cells from inactivating T cells.  The immune checkpoint inhibitors allow T cells to infiltrate cancer cells and kill them. 

Novel Idea of Epoch-making Cancer Drug Conceived by Japanese Scientists


In 1990s, Tasuku Honjyo and colleagues at Kyoto University in Japan conceived an idea of an immune checkpoint inhibitor. 


The research team found that protein PD-1 of an immune cell has a function for deactivating the attacking function to prevent itself from destroying healthy tissue using mice.


Although the research team offered Japanese pharmaceutical companies the idea of the immune checkpoint inhibitor, all the companies were reluctant to accept the offer.  Finally, the research team offered an American venture pharmaceutical company named Medarex to create an immune checkpoint inhibitor.  Medarex finally created the drug called Nivolumab (tradename: Opdivo).   


Generally, when cancer drugs are used for a long time, they cannot work for cancer cells, because they will become tolerant to the drugs.  


The immune checkpoint inhibitors do not directly attack cancer cells, but activate the immune cells so that they attack the cancer cells.  Since the immune cells can recognize various mutations of the cancer cells, they cannot escape attacks by the immune cells.   

Development of Immune Checkpoint Inhibitors


The immune checkpoint inhibitor Nivolumab (tradename: Opdivo) was jointly developed by Bristol-Myers Squibb Company (which acquired Medarex) and Ono Pharmaceutical Company (which is one of pharmaceutical companies that the research team at Kyoto University offered the concept of the immune checkpoint inhibitor).


Ono Pharmaceutical Company received approval from Japanese authorities to use Nivolumab to treat melanoma in July 2014, which was the first approval of the PD-1 inhibitor anywhere in the world.


Nivolumab received approval from FDA for the treatment of melanoma in December 2014.  

The Committee for Medicinal Products for Human Use of the European Medicines Agency recommended approval of Nivolumab for metastatic melanoma as a monotherapy in April 2015.


FDA approved Nivolumab for the treatment of squamous non-small cell lung cancer in March 2015.


FDA approved Nivolumab as a second-line treatment for renal cell carcinoma after having granted the application breakthrough therapy designation, fast track designation, and priority review status in November 2015.


FDA approved Nivolumab for the treatment of patients with classical Hodgkin lymphoma who have relapsed or progressed after autologous hematopoietic stem cell transplantation (auto-HSCT) and post-transplantation Brentuximab Vedotin in May 2016.


When the problems of prices and side effects of the cancer drugs conceived by the Japanese scientists are solved, the drugs would save intractable cancer patients all over the world.