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
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).