Abstract
PIN-2 is a novel immunomodulatory agent derivatized from a transactivator protein. We have demonstrated its activity to both stimulate and induce maturation of monocytes into dendritic cells and translational proof of principle using an aggressive metastatic murine mammary cancer model.PIN-2 initiates activity by enhancement of innate immune signaling de novo. Next Generation Sequencing of CD14+ primary human monocytes after 3-hour exposure to PIN-2 in vitro, reveals a unique profile of gene expression indicative of innate immune activation which is necessary to drive adaptive immunity towards killer T-cell immune responses. Genetic programs in the monocyte impacted by PIN-2 exposure include cytokine signaling pathways, co-stimulatory ligands, and coding and non-coding RNAs.Understanding the genetic signature of the changes by PIN-2 through the innate immune response supports the rational development of immune based combination therapies such as cell based immunotherapies and checkpoint blockade that function to modulate adaptive immunity in T-cells in a clinical setting.
Citation Format: Joshua B. Goldberg, Sophie Hanscom, Colin B. Bier. PIN-2: A novel immunopriming peptide with immunomodulatory activity linking the innate and adaptive immune systems [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 B076.