Characterization of a human CD27 agonistic monoclonal antibody for use as an agent in glioblastoma therapy (P4411)

Abstract

Abstract CD27 is a costimulatory molecule constitutively expressed on naïve T-cells, B-cells, and subsets of NK cells; signaling through CD27 has been shown to promote Th1 polarization, clonal expansion, enhanced survival of effector and memory cells, upregulation of effector molecules, and enhanced cytolytic activity. We are characterizing the use of an agonistic anti-CD27 antibody, CDX1127, as a treatment in a preclinical glioblastoma model in human CD27 transgenic mice. We have shown that in vitro stimulation of isolated T-cells from hCD27+/- mice with CDX1127, in the context of TCR signaling, leads to increased proliferation, decreased apoptosis, and increased secretion of IFN-γ and TNF-α, corroborating its agonistic activity. Furthermore, we have analyzed the efficacy of CDX1127 as a monotherapy in a mouse glioblastoma model as well as an adjuvant in a total tumor RNA dendritic cell vaccine.