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

Abstract

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