Rapid restoration of immunity in immune-suppressed cancer patients using T-cell vaccines

October 20, 2005

(Philadelphia, PA) - Patients with multiple myeloma suffer from a malignant proliferation of plasma cells in their bone marrow. The standard treatment for this form of cancer is high-dose chemotherapy and transplantation of one's own blood-producing adult stem cells; however, this aggressive treatment wipes out the mature immune-system cells of patients - leaving them vulnerable to infection.

A complementary treatment currently approved is to vaccinate myeloma patients against pneumococcus, a common bacterial infection, a year after their transplantation. But why wait a year, wondered researchers at the University of Pennsylvania School of Medicine? Their own investigation revealed that protective levels of immunity against pneumococcus could be obtained in patients who were given the prophylactic bacterial vaccine in addition to a new autologous T-cell-based vaccine only two weeks after transplantation. Indeed, protection developed in the patients within a month after the transplantation. Their clinical trial is described in this week's online edition of Nature Medicine.

"We found that we can rapidly rebuild the patients' immunity after chemotherapy and stem-cell transplant," said Carl June, MD, Director of Translational Research at Penn's Abramson Cancer Center. "For future studies, we will apply the principles learned from this study to hone the development of a cancer vaccine aimed directly at tumors and other cancers," added June, who is also Professor of Pathology and Laboratory Medicine in Penn's School of Medicine.

Early Measures Prove Highly Effective
Patients in the study were all given two pneumococcal vaccines one month and three months after their stem-cell transplants; whereas normally they would have to wait up to a year. The patients were then divided into four groups: one group received an initial pneumococcal vaccine before transplantation and chemotherapy, then a T-cell vaccine immediately after; a second group received the pneumococcal vaccine before transplantation and chemotherapy, but received the T-cell vaccine three months after their transplant and chemotherapy. The last pair of groups did not get the initial pneumococcal vaccine before the standard transplant and chemotherapy, but did receive the T-cell vaccine immediately after or three months after the standard treatment.

The researchers found that the patients in the group that received the early pneumococcal vaccine plus the early T-cell vaccine infusion had an immune response that was protective and higher than often achieved in normal patients who do not have cancer.

Custom-Designed T-Cell Therapies Will Enhance Immunity
At the recently opened Clinical Cell and Vaccine Production Facility at Penn, "we have been using new cell-based custom therapeutics derived from a patient's own T cells in this and other studies, with the long term goal of improving outcome and extending life," explains co-author Bruce Levine, PhD, who directs the Facility. T-cells are taken from a patient and expanded about a thousand fold. The engineered T-cells are then given back to the patient a few weeks later via an infusion. The newly grown T cells continue to grow in the patient, which is different than a red blood cell transfusion. The effect of this therapy is to quickly repopulate a patient's immune system with mature cells that can support immunity against infections, and potentially against tumors.

"This study showed how to take a vaccine that is a failure in people after chemotherapy and to modify it so that it works in cancer patients after chemotherapy," says June. "The surprising thing is that the vaccine works better than normal in many of the patients. This is the first step in developing a new form of personalized therapy for the treatment of cancer, where engineered T-cells will be used to boost the immune system, essentially priming it to make cancer vaccines work better."

In addition to June and Levine, study co-authors include Edward Stadtmauer from Penn and Aaron Rapoport and Alan Cross, University of Maryland.
This study was funded by the Leukemia and Lymphoma Society, the National Institute of Allergy and Infectious Diseases, the National Cancer Institute, and the Multiple Myeloma Research Foundation. This release can also be found at: www.uphs.upenn.edu/news.

PENN Medicine is a $2.7 billion enterprise dedicated to the related missions of medical education, biomedical research, and high-quality patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System.

Penn's School of Medicine is ranked #2 in the nation for receipt of NIH research funds; and ranked #4 in the nation in U.S. News & World Report's most recent ranking of top research-oriented medical schools. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.

Penn Health System comprises: its flagship hospital, the Hospital of the University of Pennsylvania, consistently rated one of the nation's "Honor Roll" hospitals by U.S. News & World Report; Pennsylvania Hospital, the nation's first hospital; Presbyterian Medical Center; a faculty practice plan; a primary-care provider network; two multispecialty satellite facilities; and home health care and hospice.

The Abramson Cancer Center of the University of Pennsylvania was established in 1973 as a center of excellence in cancer research, patient care, education and outreach. Today, the Abramson Cancer Center ranks as one of the nation's best in cancer care, according to U.S. News & World Report, and is one of the top five in National Cancer Institute (NCI) funding. It is one of only 39 NCI-designated comprehensive cancer centers in the United States. Home to one of the largest clinical and research programs in the world, the

Abramson Cancer Center of the University of Pennsylvania has 275 active cancer researchers and 250 Penn physicians involved in cancer prevention, diagnosis and treatment.

University of Pennsylvania School of Medicine

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