In a study to be published in the online early edition of the Proceedings of the National Academy of Sciences the week of Aug. 24, the researchers report that patients with high-risk acute myeloid leukemia (AML) or advanced myelodysplasia (a blood disorder) who received a cancer vaccine shortly after a stem cell transplant not only had few complications but also mounted a strong immune system attack on the disease.
Particularly encouraging was the fact that rates of graft-versus-host disease (GVHD), a potentially severe aftereffect of immune system-based therapies, were no higher than with stem cell transplants alone.
The key to the technique's success was the timing of the vaccine, explained the study's co-senior author, Glenn Dranoff, MD, of Dana-Farber. "In previous studies that have combined stem cell transplantation with a cancer vaccine, the vaccine wasn't given until a significant amount of time after the transplant," said Dranoff. "In research with animal models, we found the approach works best if the vaccine follows the transplant by just a few weeks."
The study involved 28 patients with advanced myelodysplasia or high-risk AML ("high-risk" meaning their disease did not respond to standard chemotherapy treatment). Twenty-four underwent a transplant of hematopoietic (blood-making) stem cells: after receiving chemotherapy to reduce the number of diseased blood-forming cells in their bone marrow, they received an infusion of healthy stem cells from a matched donor. The transplanted cells settled in the bone marrow, where they began to regenerate patients' blood supply, including white blood cells and other agents that constitute the immune system.
Between 30 and 45 days after transplant, 15 of the patients began receiving a cancer vaccine. The vaccine was made by surgically removing cancerous or myelodysplasic tissue from patients and genetically altering the diseased cells so they would produce a protein called GM-CSF. When these modified cells were injected into patients as a vaccine, the cells began pumping out GM-CSF. Just as a matador's cape provokes the bull to attack, GM-CSF spurred the immune system to attack cancer cells throughout the body.
Ten of the participating patients completed the full course of six vaccinations (the others had to drop out of the trial because of rapidly advancing disease). All of the patients who received even a single vaccination had a better survival rate than people with these diseases customarily have. Of the 10 who received the entire vaccine course, nine are alive and in full remission up to four years after treatment.
Although the only way to determine whether the combined transplant/vaccine approach is superior to transplant alone is to compare them head-to-head in a clinical trial, the results of the current study are highly encouraging, said co-senior author Robert Soiffer, MD, of Dana-Farber. Historically, only about 20 percent of similar high-risk AML and myelodysplasia patients who receive a transplant survive for at least two years.
Researchers believe the new approach takes advantage of the unique conditions that exist within the body shortly after a stem cell transplant. "It usually takes several months following a transplant for the new tissue to take root in the bone marrow and fully reconstitute the blood supply," said Soiffer, who is also a professor of medicine at Harvard Medical School. "The period while that reconstitution is taking place is special. The initial chemotherapy has depleted much of the patient's immune system, and the body is trying to restore its previous state of function. That 'unsettled' condition seems to be a very opportune moment for an intervention such as a cancer vaccine."
One of the pleasant surprises of the study was that GVHD rates among study participants varied little from those of transplant-only patients. As part of the transplant process, patients receive Tracrolimus, a medication that inhibits the newly implanted tissue from launching an immune system attack on the recipient's body. Researchers speculated that the drug might dampen the vaccine's ability to spark an immune response against diseased cells, but that turned out not to be a problem.
Researchers also have strong evidence that the transplant and vaccine complement each other in fighting AML and myelodysplasia cells. By analyzing the blood of patients who received the combined therapy, investigators found a sharp drop in a telltale protein, indicating cancer cells were being killed by the immune response triggered by the vaccine.
The study, though small in size, provides a solid indication that the future of cancer therapy may involve combinations of treatments -- such as chemotherapy, radiation, and surgery -- that directly kill cancer cells, and other agents -- such as cancer vaccines – that mobilize the immune system against the malignancy. "Where we currently have effective cancer therapies, they almost always involve the combination of treating the disease and the host," said Dranoff, who is also an associate professor of medicine at Harvard Medical School. "Chemotherapy and 'smart' drugs have a crucial role to play, but when cancer cells find a way around them, immune-based treatments offer another line of defense."
The study's lead author is Vincent Ho, MD, of Dana-Farber.
Other contributors include: Matthew Vanneman, Haesook Kim, PhD, Tetsuro Sasada, MD, PhD, Yoon Joong Kang, PhD, Mildred Pasek, RN, Corey Cutler, MD, John Koreth, DPhil, Edwin Alyea, MD, Stefanie Sarantopoulos, MD, Joseph Antin, MD, Jerome Ritz, MD, and Christine Canning, PA-C, of Dana-Farber; Jeffrey Kutok, MD, PhD, of Brigham and Women's Hospital; and Martin Mihm, MD, of Massachusetts General Hospital.
Support for the study was provided by the Ted and Eileen Pasquarello Research Fund, the Leukemia and Lymphoma Society, the National Institutes of Health, and Bayer Pharmaceuticals.
Dana-Farber Cancer Institute (www.dana-farber.org) is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute. It is the top ranked cancer center in New England, according to U.S. News & World Report, and one of the largest recipients among independent hospitals of National Cancer Institute and National Institutes of Health grant funding.
Bill Schaller | EurekAlert!
Smart Data Transformation – Surfing the Big Wave
02.12.2016 | Fraunhofer-Institut für Angewandte Informationstechnik FIT
Climate change could outpace EPA Lake Champlain protections
18.11.2016 | University of Vermont
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
06.12.2016 | Materials Sciences
06.12.2016 | Medical Engineering
06.12.2016 | Power and Electrical Engineering