ORLANDO"Vaccines based on characterized tumor antigens have the advantage of potential tumor specificity from the start," Ronald Levy, MD, chief, Division of Oncology, Stanford University School of Medicine, said at an ASCO satellite symposium on cancer vaccines. Development of such vaccines requires definition and isolation of a specific target, and production of the purified target antigen, he said.
In patients with B-cell lymphomas, the opportunity to create a specific vaccine is possible because of the presence of a tumor-specific antigen, in the form of a clonally expressed immunoglobulin protein present on the surface of the malignant lymphocytes.
As Dr. Levy explained, surface immunoglobulins that are present on B cells display antigenic determinants within the variable regions of their light and heavy chains. These determinants, or idiotypes, are unique because of the combinatorial process by which they are formed. Because B-cell malignancies are monoclonal, all of the tumor cells display the same idiotype. Since the chemical nature of at least the common portions of the immunoglobulin proteins is known in advance, it is possible to isolate and purify tumor-specific idiotypes, he said.
Idiotype vaccines can stimulate both cellular and humoral immune responses, Dr. Levy said. While induction of T-cell responses is an important feature for vaccines, production of an antibody response is also important, given the efficacy of mo-noclonal antibody therapies against this particular target.
"In the case of vaccines, we would like to generate a polyclonal response that would target many different aspects of the antigen, one that would have a long-lasting effect and could produce immunologic memory," he said.
The vaccines used by Dr. Levy and his colleagues to treat B-cell lymphomas are customized to individual patients. The initial approach they devised was to obtain a tumor sample from the patient and fuse the malignant B cells, which bore the target immunoglobulin idiotype antigen, with myeloma cells, to produce hybridomas. From the hybridomas, they could then isolate and purify unlimited quantities of the specific tumor antigen. To create a vaccine, the tumor antigen was combined with the carrier protein KLH (keyhole limpet hemocyanin, a strongly immunogenic protein) and mixed with an immunologic adjuvant.
In a study from Stanford, 41 patients with non-Hodgkin’s B-cell lymphomas received standard chemotherapy, then therapy with a specific idiotype vaccine derived from their individual tumors (Blood 89:3129-3135, 1997).