Translational development of active immunotherapy for hematologic malignancies

Idiotype (Id) antigen is a unique, truly tumor-specific antigen. Early preclinical studies have shown Id vaccination to be efficacious against established tumors, and this effect is enhanced by addition of the cytokine granulocyte-macrophage. One clinical study showed that injections of immunoglobulin derived from each patient's tumor cells (immunoglobulin-Id protein) induced Id-specific immunologic responses of the humoral type and/or the cell-mediated type, and that those patients who experienced cell-mediated responses achieved molecular remissions. Addition of cytokines to Id vaccination can greatly influence the magnitude and phenotype of the immune response to protein antigens. One cytokine, granulocyte-macrophage colony-stimulating factor, is particularly important to the success of cancer immunotherapy. Some studies have shown the ability of granulocyte-macrophage colony-stimulating factor to enhance protective tumor immunity and help prolong survival rates. A number of trials have been conducted on the use of Id vaccination in the treatment of follicular lymphoma. Currently, the National Cancer Institute (Frederick, MD) is conducting a large, randomized, multicenter, phase III trial comparing chemotherapy alone versus chemotherapy followed by vaccination with Id-keyhole limpet hemocyanin plus granulocyte-macrophage colony-stimulating factor. This pivotal study is the final step before vaccine therapy might be considered as an option of standard care for patients with follicular lymphoma.