Therapeutic efficacy of a fully human anti-CD27 monoclonal antibody in a murine colon carcinoma model (162.23)

Abstract

Abstract The costimulatory molecule CD27 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 effector capacity and memory in T cells; in clonal B cell expansion and germinal center formation; and in NK cell cytolytic activity. Agonistic anti-mouse CD27 mAbs have been shown to have potent anti-tumor activity. A panel of fully human antibodies recognizing human CD27 was generated and we have previously shown that our lead clone (1F5) can mediate anti-tumor effects using the BCL1 B-lymphoma line in human CD27-transgenic (hCD27-Tg) mice. In order to further investigate the mechanism of this anti-hCD27 monoclonal and its activity in a therapeutic setting we assessed anti-tumor activity using the CT26 murine colon carcinoma line. CT26 cells were delivered s.c. to hCD27-Tg animals and five doses of 1F5 were delivered to mice i.p. beginning on days 3, 5, or 7. In multiple experiments, tumor growth in mice treated with 1F5 was substantially delayed or prevented compared to that of control-treated mice. When 1F5-treated surviving mice were rechallenged with CT26 cells, without additional anti-CD27 antibody treatment, tumors did not grow in most animals. These data support the continued clinical development of this anti-CD27 mAb to enhance immune responses in cancer therapy. Investigations of immune cell subset depletions and combination therapies are ongoing.