University of Maryland researchers report improvement in infection-fighting ability within a month
A new form of immunotherapy, which combines a vaccine with an infusion of a person’s own T cells engineered in the laboratory, helps to restore cancer patients’ ability to fight infection after high-dose chemotherapy. University of Maryland cancer researchers report their findings in a study published in the November issue of Nature Medicine.
Immune deficiency is a serious problem for cancer patients, especially those who receive intensive chemotherapy prior to bone marrow transplants. Patients are at high risk of developing infections and recurrence of their cancer.
In the clinical study, patients with advanced myeloma, a cancer of the plasma cells in the bone marrow, were treated with high-dose chemotherapy and a bone marrow transplant. They received a series of vaccinations against a common bacterial form of pneumonia as well as an injection of their own laboratory-enhanced T cells, or immune cells. Researchers found the therapy was most effective when they vaccinated patients before the bone marrow transplant to jump-start the immune system and then collected the “vaccine-primed” T cells, activated them in the lab and gave them back to the patients 12 days after the transplant.
Within a month, these patients, who also received booster shots of the pneumonia vaccine, showed significant improvement in their immune response, according to Aaron P. Rapoport, M.D., an oncologist/hematologist at the University of Maryland Marlene and Stewart Greenebaum Cancer Center and the lead author of the study. The therapy not only accelerated the production of T cells, but also improved the cells’ response to the pneumonia vaccine and ability to protect the patients from infection.
“Giving these activated T cells early after transplant, followed by booster immunizations, appears to hold the key to more robust and sustained T-cell-dependent antibody responses,” says Dr. Rapoport, who is also an associate professor of medicine at the University of Maryland School of Medicine. The response to the pneumonia vaccine among patients in the study was as good as that seen in many healthy adults.
“These results are very promising and suggest that this novel approach could be used to treat others with seriously compromised immune systems, such as those with HIV and the elderly, in addition to cancer patients,” Dr. Rapoport says.
He adds that now University of Maryland researchers and their collaborators at the University of Pennsylvania School of Medicine want to combine this T-cell therapy with a cancer vaccine that would target tumor cells. “Ultimately we would like to use this type of strategy to enhance the body’s ability to develop a more effective immune response to cancer,” Dr. Rapoport says.
He says that researchers at both institutions have used activated T-cell injections using a patient’s own cells to try to boost the immunity of patients with blood cancers, but this is the first time that they have combined the therapy with any type of vaccine.
The 54 patients in the four-year clinical trial were treated at the University of Maryland Marlene and Stewart Greenebaum Cancer Center in Baltimore and the Abramson Cancer Center at the University of Pennsylvania in Philadelphia. They were divided into four groups, with each group receiving the pneumonia vaccine and an infusion of their own T cells on a different schedule.
The patients with the best immune response received one dose of the vaccine prior to their bone marrow transplant and two doses afterward. They also received the T cells significantly earlier than other patients in the study – 12 days after the transplant. Patients who received the vaccine on the same schedule, but did not receive the T cells until three months after the transplant, did not show the same response.
The University of Maryland Center for Vaccine Development was also involved in the research as was the U.S. Food and Drug Administration. Collaborators include Alan Cross, M.D., Dean Mann, M.D., Robert Edelman, M.D., and Ashraf Badros, M.D., of the University of Maryland, and Carl H. June, M.D., Bruce L. Levine, Ph.D., Edward A. Stadtmauer, M.D., and Nicole Aqui, M.D., of the University of Pennsylvania.
The research was funded by the Leukemia and Lymphoma Society of America, the National Institute of Allergy and Infectious Diseases, the National Cancer Institute and the Multiple Myeloma Research Foundation as well as gifts from the Jiji Foundation and Willard Hackerman.