Translational development of vaccination strategies in follicular NHL.

Follicular lymphoma expresses a unique immunoglobulin molecule termed idiotype that has been used as a tumor-specific antigen for vaccine development. Early stage clinical studies revealed that vaccination consisting of keyhole limpet hemocyanin-conjugated lymphoma idiotype protein in combination with granulocyte-macrophage colony-stimulating factor induced tumor-specific immune responses and molecular remission in patients with follicular lymphoma. Three double-blind, randomized, Phase III trials were conducted to further determine the clinical benefit of this vaccine therapy. Compared to the placebo, prolonged disease-free survival in vaccinated patients was concluded only in one study where all the patients enrolled in the trial already had complete remission from induction chemotherapy. Next generation idiotype vaccines are being developed with the focus on simplifying vaccine formulation and potentiating tumor-specific immunity. This category includes genetically modified idiotype single-chain DNA vaccine, liposome-encapsulated idiotype vaccine and dendritic cell vaccine. Although preclinical data supported the immunogenicity and therapeutic advantage of these new vaccines, their clinical benefits remain to be tested. Optimizing new generation idiotype vaccines may require combination with immune adjuvants that potentiate vaccine-induced antitumor immunity, have direct effects against tumor or block immune regulatory checkpoints. Moreover, identification of a universal follicular lymphoma antigen is important for future development of vaccine therapy against this disease.