Lymphoma vaccine therapy: next steps after a positive, controlled phase III clinical trial

Many of the efforts toward developing vaccines against human malignancies have been frustrated by the lack of identification of a tumor-specific antigen that would allow tumor cells to be distinguished from normal cells. Idiotypic determinants of the surface immunoglobulin (Ig) associated with a given patient's B-cell lymphoma are unique to that tumor, and can thus serve as a tumor-specific marker. When conjugated to the immune carrier keyhole limpet hemocyanin (KLH), vaccination with an idiotype protein vaccine has been able to improve length of freedom from disease relapse in patients with follicular lymphoma (FL) in a minimal residual disease (MRD) state after induction therapy, as demonstrated in a recent randomized, controlled phase III trial. In addition to predictive biomarker discovery, using residual autologous tumor and blood samples from patients vaccinated on the phase III trial, we have now developed a next generation idiotype DNA vaccine with the goal of reducing vaccine production time while maintaining efficacy. A first-in-human study is planned to evaluate its use in patients with asymptomatic phase lymphoplasmacytic lymphoma.