Dendritic Cells: A Key Target for Vaccine Science
Date & Time:
Steinman to Deliver Kinyoun Lecture at NIH
Two of Ralph Steinman’s favorite hobbies – ballroom dancing and downhill skiing – illustrate contrasting approaches to how scientists design vaccines, an endeavor in which the renowned physician immunologist is trying to bring about change.
One vision is polished and precise: the steps will lead to a specific ending every time. The other involves a constant challenge, with random happenings along the way affecting the outcome. The end is usually a question mark.
While Dr. Steinman wishes he had more time for both hobbies, he would like the emphasis of vaccine research to be more like the ballroom dance.
“Know what’s to come and then make it into a productive vaccine,” he says. “I’d rather know what the immune system is going to do and then develop the vector and adjuvants.”
Kinyoun Lecture: Dendritic Cells
Steinman, a physician, distinguished professor, and head of the Rockefeller University Laboratory of Cellular Physiology and Immunology in New York City, will deliver the 2008 Kinyoun Lecture at the National Institutes of Health (NIH) on Nov. 20 at 2 p.m. in the Masur auditorium. The title of his talk, “Dendritic Cells: A Key Target for Vaccine Science,” focuses on a career-changing finding he was part of three decades ago.
Today, about 70 percent of the research under way in Dr. Steinman’s laboratory at Rockefeller focuses on designing a vaccine against HIV. That also is the focus of the man who will be introducing Dr. Steinman in Masur, Anthony S. Fauci, M.D., director of the NIH National Institute of Allergy and Infectious Diseases, which sponsors the annual lecture.
In 2007, both Drs Fauci and Steinman received Lasker Foundation Awards for their career work, much of which has focused on finding ways to treat and prevent HIV. Dr. Steinman’s Albert Lasker Basic Medical Research Award was for discovering dendritic cells, while Dr. Fauci’s Mary Woodward Lasker Award for Public Service was for his role as the principal architect of two major U.S. governmental programs, one aimed at AIDS and the other at biodefense. Having two Lasker award winners from the same year on the same stage is rare.
Though the two have never collaborated on a research project, they are familiar with each other’s work and did “talk shop” briefly at last year’s Lasker ceremony, according to Dr. Steinman, discussing frustrating setbacks in an HIV vaccine trial.
“We have a lot in common fundamentally,” says Dr. Steinman. “We are both physicians who emphasize immunology in our studies of mechanisms for disease pathogenesis and protection.”
Dr. Fauci says it will be an honor to introduce a true scientific pioneer.
"It is very rare that an investigator makes a discovery so important that that influences virtually every aspect of a scientific discipline,” says Dr. Fauci. “Dr. Steinman's discovery of dendritic cells opens the door to advances in many areas, from vaccine development to cancer immunotherapy. His elegant work has been – and will continue to be – extraordinary in its impact."
Training the Immune System
In 1972, while studying human immune system responses, Dr. Steinman and his mentor, the late Dr. Zanvil Cohn, discovered and named dendritic cells. While the understanding of dendritic cell function is expanding, it is already evident that they have the ability to turn on or turn off areas of the immune system, thus either triggering or silencing a response.
Controlling both of those aspects of immunity has enormous potential in medicine. Ever since their seminal discovery, Dr. Steinman has devoted his career to learning how to use dendritic cells to foster beneficial immune system responses. For example, the biology of dendritic cells is now being used to explore vaccines and therapies to prevent infectious diseases, autoimmune disorders, allergy, cancer, and rejection of organ transplants.
One key to reaching those goals, says Dr. Steinman, is to shift vaccine design research from what he considers guesswork to something more reliable and predictable.
“We can’t put all our eggs in one basket and focus only on using microbes in vaccines,” says Dr. Steinman in advocating an immune system approach. “Pasteur realized that a microbe would produce protection, but he did his research prior to the development of the science of immunology.
“Not that one is right and the other is wrong. It’s just a problem of balance. Microbes have limitations and are used as the basis of a vaccine in the hope that the immune system will responds. Let’s put more emphasis on immunologic science to design vaccines in the first place.”
Of Mice and Models
Immunologic science, says Dr. Steinman, is primarily about reduction – taking cells and molecules apart, observing and understanding their different functions. Generally, however, too little focus is placed on putting those molecules back together to observe and learn about the whole system.
“That’s what we’re doing at Rockefeller and what I try to promote,” says Dr. Steinman. “How can we determine what the immune system is going to do, and then how can we control that response, not only with cells in the laboratory, but also in an animal or a patient.”
He says the whole-model approach is unappealing to many young scientists because of the additional research time involved, which translates to fewer published studies. Dr. Steinman says he still works 16-hour days, typically seven days a week.
“Look at today’s scientific journals,” says Dr. Steinman. “A huge emphasis is put on ‘model antigens’ – the antigen models something in an animal or cell. But they are not true models, not representative of what is in the real world. We use the word ‘model’ when we should use the word ‘tool,’ because these antigens have great experimental advantages.
“We need to set the standards a little higher, consider the whole immune repertoire, the whole beauty of the immune system and what it can do.”
In his research group, Dr. Steinman’s clinical team recruits volunteers into studies that pertain to cancer, HIV/AIDS, and other infectious diseases. All findings from these clinical studies are integrated throughout the 20-member lab group so everyone can share the same methods and concepts – a productive learning method he acquired from Dr. Cohn.
One promising study under way involves trying to use proteins from HIV as the major component of a vaccine. Dr. Steinman’s associates are taking the microbe apart and studying its protein antigens and other constituents that interact with immune system.
“People think we’re crazy and say that proteins are not good vaccines,” says Dr. Steinman. He shrugs off that criticism. “The bigger question is, why not? We need a new type of vaccine that uses select components of a microbe or tumor cell or other cause of disease, and administers these with other defined substances, such as adjuvants, that directly exploit immunology.”
Volunteers in his clinical studies are excited about the work, he says, but they also know that science is a slow process.
“We aren’t evangelists,” he says. “The volunteers see the importance of the research and want to be part of the process. We share hypotheses with them and let them know what we’re doing and why.”
What Dr. Steinman’s group is doing is trying to change tradition, from one vaccine delivery approach to another. And they are hoping that dendritic cells will become the maestro that leads to those new steps.