therapeutic vaccination with recombinant idiotype and rnadjuvant cures mice with pre established a20

1. Abstract 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 toidiotype 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 tumorswere intradermallyimmunized 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-timetumor eradication in a substantial percentage of vaccinated mice bearing palpable A20 lymphoma. 2. Keywords: Idiotype; Immune Response; Lymphoma; Th1; Th2; Vaccine