Evaluation of detailed biological effects of adjuvants on immune cells has been assessed in a limited number of studies performed only on samples derived from healthy individuals. No data are available on samples derived from cancer patients who may have a severe immune impairment. A novel RNA-based adjuvant (RNAdjuvant® developed by CureVac) is made of a synthetic single stranded RNA molecule combined with a polymeric carrier. It is known to interact with toll-like receptors (TLRs) 7. The effects of RNAdjuvant® on PBMCs of liver cancer patients was assessed in an ex vivo setting, using a multiparametric approach to analyze network dynamics of early human immune responses. PBMCs were obtained from 8 healthy volunteers and 17 HCC patients enrolled in the present study. After treatment in culture, the effects of RNAdjuvant® were assessed by evaluation of CD80, CD86 and HLA-DR expression, pattern of cytokine production as well as gene expression profile. Moreover, the downstream effect on CD4+ T cell phenotyping was evaluated. The TLR4 ligand LPS was used as comparison. Treatment with RNAdjuvant® showed comparable effects on PBMCs of both HCC and healthy subjects, as shown by all the evaluated parameters. CD80, CD86 and HLA-DR expression was found upregulated in circulating dendritic cells, which promoted a CD4+ T cell differentiation towards an effector phenotype. A mixed Th1/Th2 cytokine pattern was induced in PBMCs, although a more predominant production of TNFα and IFNγ was observed in HCC patients vs. healthy controls. The cytokine profile was further confirmed by gene transcriptional analysis, which showed up-regulation of several genes involved in innate and adaptive immune-related pathways.
Citation Format: Luisa Circelli, Annacarmen Petrizzo, Maria Tagliamonte, Regina Heidenreich, Maria Lina Tornesello, Franco M. Buonaguro, Luigi Buonaguro. Immunological effects of a novel RNA-based adjuvant in liver cancer patients [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A044.
- ©2016 American Association for Cancer Research.