Nobel researcher was a subject of his own discovery

LONDON/CHICAGO (Reuters) - Ralph Steinman proved the importance of his Nobel prize-winning research in a most personal way, using his own discoveries to fight the pancreatic cancer that eventually killed him just days before the award was announced.

In the future, millions more people around the world are likely to gain from the findings of the Canadian-born scientist and his two fellow laureates -- American Bruce Beutler and Jules Hoffmann of France -- into the workings of the body's highly complex immune system.

Steinman, 68, died on September 30 after being diagnosed with pancreatic cancer four years ago. His life was extended by a treatment of his own design, using the defensive dendritic cells that he discovered in 1973, according to New York's Rockefeller University.

Steinman's case shows how a better understanding of the immune system is unlocking new ways of preventing and treating common diseases -- from bacterial infections to cancer.

The breakthroughs in pinpointing these defensive elements have helped reignite interest in vaccine research in recent years by shedding light on the twin-track process of early and late -- or innate and adaptive -- immunity that protects our bodies from invaders.

Hoffmann and Beutler made major discoveries in describing various components of the innate or early immune system, a primitive part of the immune system that is the body's first line of defence against foreign invaders.

Steinman made a major contribution in discovering a particular cell, the dendritic cell, a major player in the adaptive immune system that kicks in later with custom-made weapons like antibodies to fight off infection.

"If you put those discoveries together, you have a very substantial piece of work which adds great insight into our understanding of the immune system in general and how the immune system fights infections," said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases division of the National Institutes of Health.

"All of those things are made possible by understanding the mechanisms whereby the body utilizes both the innate and adaptive immune system," Fauci said.

That has proved pivotal in the development of improved vaccines in the past decade, said Vincent Brichard, head of immunotherapeutics at GlaxoSmithKline's vaccines unit.

"A new generation of therapeutic vaccines may enable us to treat a number of major cancer types," Brichard said.

FIGHTING PROSTATE CANCER

While Steinman's treatment for his own cancer may have been self-made, the world's first therapeutic vaccine to fight tumours was actually launched last year.

Dendreon's Provenge is a novel kind of drug for prostate cancer, tailored to each patient, that works by stimulating the person's immune system to fight tumours. It has met with limited commercial success but is an important proof of the concept.

Similar treatments are now in development at several bigger companies, including GlaxoSmithKline, which has a closely watched experimental vaccine for lung cancer in late-stage clinical trials.

"His discovery of dendritic cells has opened a huge understanding of how the immune system works and how it regulates its response to viruses and bacteria and also to cancer cells that start growing in the body," said Dr. Raymond DuBois of the University of Texas M.D. Anderson Cancer Centre, where Steinman served as an adviser to the immunology centre.

DuBois said cancer is an immune-privileged system in that it evades most of the immune system's defences.

"By understanding how the immune system works, we can engineer treatment plans and antibodies so we can retrain the immune system to attack the cancer," DuBois said.

Research by Beutler and Hoffmann sheds light on innate immunity, which kicks in much more rapidly than adaptive and is shared between humans and all other animals.

It was only in the 1990s, that Hoffmann's work in fruit flies and Beutler's work in mice showed how this system uses proteins called Toll-like receptors or TLRs to fight germs.

Harnessing TLRs is today a growing focus for biotech and pharmaceutical companies looking for treatments for a wide range of illnesses from cancer to respiratory and inflammatory diseases.

The immune system's main function is to protect against harmful invaders but it can sometimes go into overdrive and attack healthy tissue, leading to autoimmune inflammatory diseases, such as type 1 diabetes, multiple sclerosis, rheumatoid arthritis and inflammatory bowel disease.

"Almost all vaccines against microbes, vaccines against cancer, and vaccines to try to eliminate and down-regulate immunity in inflammatory diseases are based on these discoveries," said Lars Klareskog, chairman of the Nobel Assembly. (Additional reporting by Mia Shanley in Stockholm; Editing by Michele Gershberg and Cynthia Osterman)

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