Using T-Cell-Based Vaccines, Penn Researchers
Achieve Rapid Restoration of Immunity
in Immune-Suppressed Cancer Patients
Novel Approach Reduces the Time to Achieve Protective Levels
in Myeloma Patients by Nearly One Year
(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
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.
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
The University of Pennsylvania 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;
Penn 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.