Vaccine therapy for B-cell lymphomas: next-generation strategies

Active immunotherapy is a promising approach for the treatment of lymphomas. Immunization with the clonal tumor immunoglobulin, idiotype, expressed on the surface of B-cell malignancies was associated with induction of tumor-specific cellular and humoral immunity, molecular remissions, and prolonged disease-free survival in early clinical trials. Idiotype vaccination was also demonstrated to induce tumor-specific T-cell immunity in the absence of B cells following treatment with rituximab-containing chemotherapy, suggesting that vaccines may be used in combination with rituximab. Three double-blind randomized phase 3 idiotype vaccine trials are currently ongoing to definitively determine the clinical benefit of idiotype vaccination in patients with lymphoma. Novel second-generation lymphoma vaccines are in development to streamline the production of patient-specific cancer vaccines and show encouraging results in preclinical and pilot clinical studies. To enhance the clinical efficacy of active immunotherapy, future clinical trials are likely to use a combination strategy with the lymphoma vaccine to stimulate an antitumor T-cell response and the simultaneous suppression of immune regulatory pathways to augment the induced T-cell response.