Vaccine Therapy for Patients with Recurrent Blood Cancers
Name of the Trial
A Pilot Trial of WT1 Peptide-Loaded Allogeneic Dendritic Cell Vaccine and Donor Lymphocyte Infusion for WT1-Expressing Hematologic Malignancies (NCI-08-C-0051). See the protocol summary.
Dr. Alan S. Wayne, NCI Center for Cancer Research
Why This Trial Is Important
Many patients, including children, with hematologic malignancies—leukemias, lymphomas, and other blood or bone marrow diseases—are treated with allogeneic hematopoietic stem cell transplantation (HSCT). In allogeneic HSCT, blood stem cells from a genetically similar donor are infused into a patient’s bloodstream after he or she has been treated with preparatory chemotherapy or radiation therapy. Although allogeneic HSCT is often initially successful in treating hematologic malignancies, residual disease sometimes remains, and many patients see their cancer return (recurrent cancer).
The success of allogeneic HSCT depends not only on the infused stem cells but also on the accompanying immune cells, such as T lymphocytes and natural killer cells, that are present in the infused material. These T lymphocytes can recognize cancer cells as being foreign and produce a beneficial graft-versus-tumor/leukemia (GVL) effect. Consequently, researchers are studying ways to safely enhance the GVL effect to protect against relapse, treat persistent disease, and improve disease-free survival after allogeneic HSCT. One approach being investigated is to infuse patients with additional donor T lymphocytes. The use of anticancer vaccines to generate more specific anticancer immune responses is also being studied.
One method of anticancer vaccine preparation is to isolate white blood cells called mononuclear cells and mature them in the laboratory into immune cells called dendritic cells, and then expose the dendritic cells to protein molecules that are found primarily in cancer cells. The dendritic cells will take up the molecules (known as tumor antigens), process them, and display them on the cell surface, where they will be “visible” to other immune cells. Then, the dendritic cells are injected into the patient, where they will hopefully stimulate an immune response that selectively targets and kills cells that have the target molecules.
In this phase I/II trial, patients will be treated with donor T-lymphocyte infusions and a dendritic cell vaccine that is designed to trigger an immune response against cells producing a protein called Wilms tumor 1 (WT1). WT1 is produced by cells of many hematologic malignancies. Vaccines targeting this protein have shown promise in animal and some human studies.
Patients will be treated with the WT1 vaccine every 2 weeks for a total of 6 doses. They will receive donor lymphocyte infusions every 4 weeks for a total of 3 infusions. The researchers will assess the safety of the treatments and determine whether they cause any side effects. Immune system responses and anticancer effects will also be measured.
“Patients with hematologic malignancies who relapse after transplantation will commonly get infusions of lymphocytes if their original donor is willing and available to donate again,” said Dr. Wayne. “By adding a vaccine, we are trying to provide a ‘one-two punch’ and generate a more potent and specific anticancer immune response.”
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