SA-4-1BBL and monophosphoryl lipid A as a novel adjuvant system with potent therapeutic efficacy against cancer in the absence of detectable toxicity and autoimmunity (P4334)

Abstract

Abstract Although subunit cancer vaccines based on tumor associated antigens (TAAs) are attractive as treatment modalities, they have limited therapeutic efficacy due to their weak immunogenicity and tumor immune evasion mechanisms. Adjuvants with potent immune stimulatory activities as component of TAA-based vaccines can overcome these limitations. In this study, we used the combination of a novel SA-4-1BBL costimulatory molecule and Toll-like receptor 4 (TLR 4) agonist monophosphoryl lipid A (MPL) with distinct mechanisms of action as a novel adjuvant system and HPV E7 as TAA in a mouse cervical cancer model. A single immunization resulted in eradication of 100% of established E7 expressing TC-1 tumors. The combined adjuvant therapy required CD8+ T cells and IFN-γ responses for efficacy. Importantly, the efficacy of the vaccine was achieved in the absence of detectable toxicity and autoimmunity as assessed by liver enzymes, blood urea nitrogen, alteration in the number of T cells, B cells, NK cells, NKT cells, macrophages, and dendritic cells, histology of major tissues, gross anatomical evidence of organ toxicity, and antibodies against ssDNA as a sign of autoimmunity. Taken together, these data demonstrate the utility of SA-41BBL/MPL as a novel adjuvant system for the development of therapeutic TAA-based subunit cancer vaccines in the absence of detectable toxicity and autoimmunity.