May 24, 2005
Cancer vaccine center opens at Dana-Farber to seize the moment in scientific research
Dana-Farber physicians Glenn Dranoff, Ellis Reinherz, and Jerome Ritz will help lead the new cancer vaccine center.
Convinced that science now has the tools to strengthen and sharpen the immune system's natural attack on cancer, Dana-Farber is launching a Cancer Vaccine Center, where laboratory research will be joined with studies of the latest treatments in patients.
The center, which consists of laboratories both on and off DFCI's central campus, is closely aligned with the Institute's Strategic Plan, which aims to conquer at least one form of cancer by 2014 through collaborative research and an emphasis on practical uses for scientific advances.
"The idea is to bring together Dana-Farber's existing programs in vaccine-related research and point them toward a common purpose," says Ellis Reinherz, MD, of Medical Oncology, who conceived of the new center and serves as its director. "The focus will be squarely on 'translating' our growing knowledge of the immune system into clinical practice."
The center's creation comes at a time of unprecedented discovery in immunology, both in the field as a whole and in its relation to cancer. Breakthroughs have revealed, as never before, the molecular landscape in which the body's immune system — the collection of organs, tissues, and cells that work to ward off infection and disease — identifies, targets, and mounts an assault on cancer cells. Researchers also have gained new insights into the "control loop" that monitors the intensity and duration of the immune response.
"We've reached a point where it's possible to use this knowledge to design vaccines in a more directed, rational way," Reinherz says, "and to rapidly test their effectiveness in patients. The idea behind the center is to draw on faculty and resources from a variety of areas and disciplines, and take advantage of the different perspectives they offer."
Ellis Reinherz, MD
The immunity community
Cancer vaccines, like all vaccines, work by raising the body's natural shield of immunity against illness. Unlike vaccines for measles or chicken pox, however, those for cancer are designed to treat disease rather than prevent it.
Doctors have long known that tumors are susceptible to attack from the immune system, but that the attack often fizzles out, leaving residual cancer cells to grow and proliferate. The reason for this shortfall is that cancer cells and normal cells look deceptively alike. The immune system, trained from birth to leave normal, healthy tissue alone, occasionally fails to recognize malignant cells and retreats too soon.
Vaccine researchers at DFCI and elsewhere have tried several approaches to boosting the immune response to cancer. They've made individualized treatments that use patients' own tumor cells, altered in a lab, as "bait" for natural disease-fighting cells. They've also fused cancer cells to so-called "presenting" cells that magnify cancer's presence on the immune system's radar.
Although these efforts and others have produced encouraging results — including complete remissions in some patients — they have been limited by sizable gaps in science's understanding of immunological processes.
The immune system's encounter with cancer takes place against a backdrop of almost incalculable complexity. All cells are covered by tens of thousands of protein fragments called antigens, which help the immune system determine whether cells are healthy (and to be ignored) or diseased (and to be killed). The antigens on cancer cells differ from those on normal cells, but often in subtle and minute ways. Different types of cancer — sometimes different cells within the same tumor — have different antigen patterns. Investigators were left to ponder: Which antigens clue the immune system to the fact that a particular cell is cancerous? Do some antigens or groups of them form a clearer cancer signal than others? If so, how?
Equally mysterious were the factors that determine the vigor and scope of the immune response. An intricate group of regulatory circuits informs the immune system about the state of battle against cancer and influences whether the attack is stepped up or scaled back. How do these circuits function, and what are their components? Why does the immune system sometimes suspend its attack prematurely? Can the regulatory signals be adjusted to extend the battle?
Glenn Dranoff, MD
Answering questions like these would enable scientists to design vaccines that zero in on even the most cleverly camouflaged cancer cells and continue until the job is finished. Over the past 10 years, advances in immunology and technology have combined to make such approaches possible. Researchers can now sort through thousands of tumor antigens to assess which exert the strongest "pull" on the immune defenses. They can determine, with growing precision, the individual sections of antigens that interlock with immune system cells. And they have the ability to measure, within days of administering a vaccine to a patient, the degree of immune response it triggers.
"We now have a rich repository of ideas and approaches that can be developed and tested in patients," says Medical Oncology's Glenn Dranoff, MD, a vaccine researcher who will lead the clinical trials component of the new center. "The goal is to conduct well-conceived, well-designed trials with a wide variety of patients, and to analyze treatment results with the most modern immunological tools to determine if vaccination is successful."
The new focus on basic mechanics of the immune response means the vocabulary of vaccine researchers increasingly resembles that of chemotherapy experts. Just as drug developers now speak of "targeted" therapies aimed at particular genetic flaws in cancer cells, many vaccine scientists view their work in terms of the accuracy with which immune defenses can be aimed at cancer.
Glenn Dranoff, MD
Core of support
The vaccine center at Dana-Farber is organized around two groups of core facilities that support research throughout the Institute. The first group, dubbed "human immunology cores," includes four labs headed by Ellis Reinherz: Bioinformatics, Mass Spectrometry, Structural Immunology, and Immune Monitoring.
The second set of core facilities, directed by Medical Oncology's Jerome Ritz, MD, focuses on clinical trial support: Vaccine Manufacturing, Clinical Reagents, Clinical and Regulatory Support.
Rewiring circuits
Researchers affiliated with the new center are pursuing several approaches to new therapies. While some of these are classic "vaccine" techniques — creating an upsurge in T cells and other segments of the immune system — others build on science's growing knowledge of immunity's command-and-control circuits.
"Knowing the rules that underlie these regulatory circuits could be useful across several types of cancer," Glenn Dranoff observes. "There are techniques that can be tested for blocking the signals that shut down the immune response to cancer too early."
Another promising avenue — an outgrowth of techniques already used in some bone-marrow and stem-cell transplants — is known as "adoptive immunotherapy." Here, patients are infused with T cells engineered to recognize specific antigens associated with cancer.
Although the vaccine center will draw on a range of basic, laboratory research, its focus is on "early-stage" clinical trials — studies where new treatments are first tested in patients. "Our aim is to establish the 'proof of principle' for novel forms of treatment," Dranoff states. "We view the center as a proving ground, the first step in the development pathway for immune-based therapies."
The directorship of the center will rotate among Reinherz, Dranoff, and Ritz. "Rather than supporting any individual's research, the center will draw on the expertise and backgrounds of people throughout the Institute," Ritz explains. "By working across disciplines, we can take advantage of new knowledge and perspectives and apply these concepts to several diseases simultaneously."