Abstract 4560: Anti-tumor activity of a fully human anti-CD27 monoclonal antibody in a transgenic mouse model

Abstract

Abstract The costimulatory molecule CD27 is a member of the 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 an important role in the activation, proliferation, survival, and maturation of effector capacity and memory in T cells; in clonal B cell expansion and germinal center formation; and in NK cell cytolytic activity. Previous published work demonstrated that agonistic anti-mouse CD27 mAbs, given without a DC maturation signal, have 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 CD27. These anti-CD27 mAbs showed specific and high affinity binding to recombinant CD27 and CD27-expressing lymphoma cells. Human CD27-transgenic (hCD27-Tg) mice were generated to evaluate the anti-CD27 mAbs in vivo. The CD27-Tg mouse line was back-crossed onto a Balb/c background in order to assess anti-tumor activity using the BCL1 B-lymphoma line. Approximately 107 BCL1 cells were delivered i.v. to backcrossed animals on day 0. Doses of 150 to 600 ug of our lead anti-CD27 mAb (clone 1F5) were delivered to mice i.p. on days 3, 5, 7, 9 and 11. In multiple experiments, tumor growth in mice treated with the anti-CD27 mAb 1F5 was substantially delayed compared to that of control-treated mice. Further, many anti-CD27 treated animals did not show evidence of tumor growth several weeks past the point where all control animals had been euthanized. These data confirm that anti-human CD27 mAbs can mediate similar anti-tumor effects as the anti-mouse CD27 agonist antibodies. The 1F5 antibody was also demonstrated to cross-react with CD27 from cynomolgus monkeys, and in a small pilot study was well tolerated and without evidence of significant lymphocyte activation. Taken together the data support the therapeutic potential of this anti-CD27 mAb to enhance immune responses in cancer therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4560. doi:10.1158/1538-7445.AM2011-4560