Cancer immunotherapy formulation · Opdivo

Cancer immunotherapy formulation · Opdivo


Sky of October


Kyoto University of Japan, Special professor Tasuku Honjyo would be received the Nobel Prize in Physiology or Medicine Prize. About “Discovery of ‘PD-1 antibody’ that utilizes immune cells which human body have original for cancer treatment”, and this is the reason that Honjyo professor would be received the Prize, this article is describing its mechanism. This article is a part of Japanese version’s blog of April 23, 2018, and its blog states opinions to a report which a securities analyst performed rating on April 17, 2018 for the stock price of Ono Pharmaceutical Co., Ltd. in Japan. This article would introduce Honjyo professor’s achievements and introduce the challenges of cancer immunotherapy which is the current research subject.


A.Opdivo (Nivolumab)


1.Opdivo (Nivolumab) is an anti-cancer drug developed by Ono Pharmaceutical Co., Ltd. together Bristol-Myers Squibb Company (Hereafter, abbreviated as BMY Company). What is revolutionary is that in the past anti-cancer treatment was mainly based on resection and chemotherapy or scientific therapy, but Opdivo (Nivolumab) is an immunotherapy that helps the human body inherent immunity. This is the first formulation in the world to be made by “PD-1 antibody” which Kyoto University’s Professor Tasuku Honjyo would be discovered.


2.When cancer cells are formed, the human immune cells (killer) T cells attack cancer cells and are coming to keep the human body a normal state. At this time, a substance (receptor) called “PD-1” is expressed on the T cell surface. However, in order to protect cancer cellselves from T cells, cancer cells express specific substances (ligands: substances that specifically bind to specific receptors) on the surface of cancer cells, bind T cells, cancer cells try to take in T cells. The ‘ligand’ which this cancer cells issue is a substance called “PD-L1, PD-L2”. And then, when the “PD-1” receptor of the T cell binds to the ligand “PD-L1, PD-L2″ of the cancer cell, the T cell stops attacking the cancer cell, allow growth of cancer.


3.”PD-1 antibody” prevents T cell receptor “PD-1” from binding to ligand “PD-L1, PD-L2” of cancer cells and makes its original immune function of T cells exert. This is called immunotherapy. However, at this time, when T cells head for other organs and cells, side effects of autoimmune diseases occur.


B.Issues of Cancer Immunotherapy


1. The following is a summary of the research subject of “PD-1” project team of Kyoto University Graduate School, School of Medicine, Immune and medicine laboratory (Honjyo laboratory).


a.Response efficiency of the therapeutic effect with the ’PD-1 antibody’ alone is 20 to 30%.


b.Depending on cancer type, combined use of “CTLA-4 antibody” dramatically improves the response efficiency of the treatment to 50~60%.


“CTLA-4 antibody”; There is a substance called “CTLA-4” that suppresses the action of T cell which exists as a receptor of T cell similar to PD-1 receptor. “CTLA-4 antibody” binds to this CTLA-4 receptor, suppresses the action of CTLA-4, and activates the action of T cells. The PD-1 receptor binds to and is taken up by cancer cells, but the CTLA-4 receptor binds to macrophages or substances called CD80, CD86 of dendritic cells and becomes inactive. This “CTLA-4 antibody” was commercialized as Yervoy (ipilimumab) by BMY Company.


c.About patient who is unresponsive to “PD-1 antibody” therapy, this cause hasn’t been discovering yet.


d.The mechanism of response / nonresponse to “PD-1 antibody” and the development and exploration of biomarkers to distinguish it are important.


e.Immune responses of PD-1 are deeply involved in metabolism and are important for maintaining the fundamental homeostasis of life.


f.From now on, it is necessary to understand the principle of life phenomena from a new viewpoint fusing immunity and metabolism.