Successes, failures and new perspectives of idiotypic vaccination for B-cell non-Hodgkin lymphomas.

The idiotype of B-cell non-Hodgkin lymphomas has been intensively investigated for its proven immunogenicity as a promising cancer vaccine. Indeed, available data clearly indicate that these vaccines are able to induce tumor-specific immune responses and molecular remissions in patients with follicular lymphoma. However, only one of the three phase III trials performed so far demonstrated a prolonged disease-free survival in vaccinated patients. The observed failures have been mainly ascribed to defects in the study design and not to the limited efficacy of idiotype vaccines per se. Therefore, innovative and optimized idiotype-based vaccine formulations are being developed in order to overcome current limitations and improve the clinical benefit of this immunotherapeutic strategy. Among the most promising advances, the development of "off-the-shelf" vaccines appears of particular relevance, being potentially able to overcome the limitations related to the complex, time-consuming and expensive production of the individualized idiotypic vaccines currently used. Moreover, there is a pressing need to identify biomarkers suitable for the identification of the subset of patients who are most likely to benefit from vaccination. Recent findings also indicate that idiotypic vaccines may be safely and successfully used in additional clinical settings, including lymphoma patients after high-dose chemotherapy and autologous stem cell transplantation.