Abstract 5343: Development of novel anti-CD27 human antibodies with therapeutic potential

Abstract

Abstract The costimulatory molecule CD27 is a member of the tumor necrosis factor (TNF) receptor superfamily, and is constitutively expressed on the majority of mature T cells, memory B cells, and a portion of NK cells. The interaction of CD27 with its ligand CD70 plays key roles in T cell activation, proliferation, survival, maturation of effector capacity and memory; in clonal B cell expansion and germinal center formation; and in NK cell cytolytic activity. Previous reports have shown that antigen-specific CD8+ cytolytic T cell immunity can be augmented through CD27 activation in mice. Of particular relevance is the work by M. J. Glennie et al. demonstrating that an agonistic anti-mouse CD27 mAb given without a DC maturation signal has potent anti-tumor activity through boosting of T cell immunity. To explore the therapeutic potential of this target, a panel of fully human antibodies recognizing human CD27 was generated using human Ig transgenic mice immunized with recombinant human CD27. These human anti-CD27 mAbs showed specific and high affinity binding to CD27 and CD27-expressing lymphoma cells. We generated transgenic mice that express human CD27 (hCD27-Tg) to evaluate the anti-human CD27 mAbs in vivo. The expression profile and regulation of the human CD27 transgene driven by its own promoter were similar to that observed with endogenous mouse CD27. Administration of anti-human CD27 mAbs in combination with ovalbumin greatly enhanced antigen specific T cell responses compared to ovalbumin plus human IgG1 isotype control in the hCD27-Tg mice. The SIINFEKL-specific CD8+ T cell proliferation and activation were detected by pentamer staining and IFNγ ELISPOT analysis. These data support the further development of these novel human anti-CD27 antibodies and we are currently investigating their therapeutic activity using various in vivo tumor models. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5343.