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Idiotypic vaccination for Follicular Lymphoma (FL) has shown clear proof of principle of biological and clinical efficacy, as well as of clinical benefit, in early-stage clinical studies. Clinical benefit, however, has been partially confirmed only by one of three randomized clinical trials. As a variable fraction of patients per trial fails to respond to idiotype vaccines, it remains paramount to improve their overall formulation. In pre-clinical models, current vaccination strategies provide a certain degree of protection, but have never shown curative potential. Previous studies have demonstrated the immune-stimulatory adjuvant effects of Toll-Like Receptor (TLR) ligands, such as synthetic double-stranded RNA. In this work, a new-generation TLR ligand adjuvant named RNAdjuvant® was evaluated. In order to study the effects of this novel adjuvant on the induction of anti-idiotypic immune responses, Balb/c mice with pre-established, palpable tumors were intradermally immunized with a recombinant A20 lymphoma idiotype vaccine incorporating RNAdjuvant®. Compared to idiotype vaccine formulations repeatedly tested in clinical trials, the new vaccine formulation enhanced a balanced immune response with special emphasis on Th1 response. Moreover, T-cell depletion studies indicated that CD8-positive T cells are indispensable for tumor rejection and improved survival. Crucially, we were able to document for the first-time tumor eradication in a substantial percentage of vaccinated mice bearing palpable A20 lymphoma.

Therapeutic Vaccination with Recombinant Idiotype and RNAdjuvant®Cures Mice with Pre-Established A20 Lymphoma