Researchers at The University of Texas M. D. Anderson Cancer Center and the National Cancer Institute have found that an experimental vaccine can prime the immune system to help fight an aggressive form of lymphoma, even though prior therapy had eliminated virtually all of the B cells thought necessary to mount such a defense.
Their study, published in the September issue of Nature Medicine, has both important basic science and clinical implications, researchers say. It demonstrates that few, if any, B cells are needed to trigger an effective T-cell immune response - a finding which overturns the commonly accepted notion that both are needed to prime the human immune system.
Their research also tests the use of personalized vaccines to help lymphoma patients fend off a recurrence of their cancer after treatment. Several such cancer vaccines are in human testing. In this study, conducted at the Center for Cancer Research, National Cancer Institute, treatment with a B-cell depleting treatment regimen followed by an experimental vaccine resulted in an impressive 89 percent survival rate at 46 months for 26 patients with mantle cell lymphoma, which is difficult to control.
"This is the first human cancer vaccine study to see T-cell responses in the absence of B cells, and this paves the way to use vaccines in a number of hematological cancers that are treated by eliminating diseased B cells," says the study's first author, Sattva Neelapu, M.D., an assistant professor in the Department of Lymphoma at M. D. Anderson.
Those cancers include forms of lymphoma and leukemia in which the cancer evolves in B-cell lymphocytes, white blood cells whose job is to produce antibodies that activate a response by the immune system. New treatments, such as rituximab, are designed to completely wipe out diseased (as well as healthy) B cells and can prolong patient survival. However, because researchers were concerned that B-cell depletion from rituximab may impede immune responses to cancer vaccines, and animal studies were contradictory, rituximab has been omitted from lymphoma vaccine studies, according to Wyndham Wilson, M.D., Ph.D., the study's principal investigator and Chief, Lymphoid Malignancies Therapeutic Section, NCI.
This question has now been answered, says senior author Larry Kwak, M.D., Ph.D., professor and chair of the Department of Lymphoma at M. D. Anderson. "We were frankly surprised to find that B cells were coming back in patients that were already primed to fight their tumors," he says. "Now we know B cells are not needed for T-cell immunity."
The study was designed to address the immunological effects of B-cell depletion and to assess the use of idiotype vaccine in mantle cell lymphoma, a rare type of non-Hodgkin's lymphoma for which there is no effective long-term therapy - the majority of patients relapse and succumb to their disease. Kwak helped develop the vaccine while he worked at the National Cancer Institute (NCI) before moving to M. D. Anderson. The so-called "idiotype" vaccine is tailored to each patient, based on the specific antigens present on the outside of the diseased B cells. The vaccine is designed to alert a patient's immune system to those antigens, and train it to destroy these cells whenever they appear.