Researchers learn to rapidly rebuild immunity in immune-suppressed cancer patients

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.

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.

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.