2018 Nobel Prize Medicine

2018 Nobel Prize Medicine

The 2018 Nobel Prize for Medicine has just been awarded to James P Allison from the United States and Tasuku Honjo from Japan, for their work on a new approach to cancer treatment. What is unique and noteworthy of this work is that it seeks to use the human immune system to combat cancer. Clearly there is a huge potential for this work to improve the human condition. In fact this work has lead to a number of lives saved and is driving thinking into a  whole new area of immuno-driven cancer therapy. All previous types of cancer therapy were directed at the tumor cell, but Allison’s and Honjo’s approach was to remove brakes that keep the immune system in check, unleashing it against tumor cells. These “checkpoint inhibitor” therapies have greatly increased survival of cancer patients and may produce even greater results when combined with traditional therapies.

Specifically Allison’s and Honjo’s work focused on mediating the performance proteins in the immune system that prevents the body’s T-cells, from attacking tumors effectively. This approach differers from the conventional Science of Self/Non-Self determination because it uses the activation of T-cell checkpoint proteins to counter the cancer mechanism of “hiding in plain sight”. Cancer relies on a bag of tricks to hide from the body’s disease-fighting apparatus. Tumors have evolved to co-opt “checkpoint” proteins found on the immune system’s T cells. These proteins normally prevent the immune system from running amok. However the cancer cells mimic these control proteins to turn the bodies  T cells from an active cancer fighting mode to a quiescent state and then the cancer takes full advantage.  New treatments and new drugs that disable these checkpoint proteins are showing significant ability to activate T cells and, in so doing, remove the cancer’s cloak of invisibility and hence its protection. It is also important to realize that this is a combination approach. Allison studied the CTLA-4 protein which scales back or  “slows down the immune system” and its cascade response to the tumor.  Tasuku Honjo had studied another protein, PD-1, which also serves as a brake, but on a completely different mechanism. The two researchers then tried to modify the behavior of each of these proteins to destroy the tumors through immune response, but by combining the action on CTLA-4 and PD-1 on malignant cells, the treatment is the most impressive, said the Nobel Committee.

In the figure, the green curve shows the effectiveness of the CTLA-4 based treatment. Blue is PD-1 and yellow is combined effect on both proteins. This combination treatment allows more than two thirds of patients to survive. Results that could be further improved in the future, if this treatment is coupled with other existing ones. In the last year, additional studies testing a few these drugs have produced unprecedented results against melanoma a very common and deadly kind of skin cancer , where traditional therapies have limited effect. It has also showed measurable gains in cancer cell reduction against other malignancies.  The work of James P Allison and Tasuku Honjo has enormous clinical implications for many different types of cancer  including those which are difficult to treat with conventional therapies, such as lung and renal cancer!

BIOVIA the science brand within the Dassault Systèmes family provides a range of solutions around the design of large and small molecule therapeutics. World renown scientists such as Martin Karplus (himself a Nobel Prize winner)  has specialized in the development of models and systems for predicting both shape and dynamical behavior of proteins and the docking of small molecules to them. In addition BIOVIA has developed  the Biologics Safety Profiler App., which enables researchers and developers to evaluate and improve the safety of biomolecules (peptides and proteins) in development.

Key features of this technology include:

  1. The Prioritization of biomolecules with respect to the Immunogenicity risk.
  2. Cartography of the HLA-binding potential along the biomolecule’s sequence.
  3. The Determination of the best substitutions to reduce the Immunogenicity

In summary this fantastic work has shown the way towards the long sought goal of human self-imuno driven cancer therapy and treatment.

James P. Allison was born 1948 in Alice, Texas, USA. He received his PhD in 1973 at the University of Texas, Austin. From 1974-1977 he was a postdoctoral fellow at the Scripps Clinic and Research Foundation, La Jolla, California. From 1977-1984 he was a faculty member at University of Texas System Cancer Center, Smithville, Texas; from 1985-2004 at University of California, Berkeley and from 2004-2012 at Memorial Sloan-Kettering Cancer Center, New York. From 1997-2012 he was an investigator at the Howard Hughes Medical Institute. Since 2012 he has been professor at University of Texas MD Anderson Cancer Center, Houston, Texas and is affiliated with the Parker Institute for Cancer Immunotherapy.

Tasuku Honjo was born in 1942 in Kyoto, Japan. In 1966 he became an MD, and from 1971-1974 he was a research fellow in the USA at Carnegie Institution of Washington, Baltimore and at the National Institutes of Health, Bethesda, Maryland. He received his PhD in 1975 at Kyoto University. From 1974-1979 he was a faculty member at Tokyo University and from 1979-1984 at Osaka University. Since 1984 he has been professor at Kyoto University. He was a faculty dean from 1996-2000 and from 2002-2004 at Kyoto University.

About the Author:

Michael Doyle
Senior Scientist for Industry Applied Materials
Dassault Systèmes