R707, a fully human antibody directed against CC ‐chemokine receptor 7, attenuates xenogeneic acute graft‐versus‐host disease

Acute graft‐versus‐host disease ( aGVHD ) remains a barrier to the success of allogeneic hematopoietic stem cell transplantation ( HSCT ). Previously, we demonstrated that CC ‐chemokine receptor 7 ( CCR 7) is critical for aGVHD pathogenesis but dispensable for beneficial graft‐versus‐leukemia responses. As a result, we evaluated a fully human anti‐ CCR 7‐blocking antibody as a new approach to prevent aGVHD in preclinical models. Here we report that antibody R707 is able to block human CCR 7 signaling and function in vitro in response to its 2 natural ligands. The antibody was less active against the murine orthologue, however, and failed to substantially limit aGVHD in a standard murine allogeneic HSCT model. Nevertheless, R707 significantly reduced xenogeneic aGVHD induced by human peripheral blood mononuclear cells ( PBMC s). R707 limited CD 4 + and in particular CD 8 + T cell expansion during the period of antibody administration. These effects were transient, however, and T cell numbers recovered after antibody cessation. R707 did not substantially impair the antitumor potential of the PBMC inoculum as antibody‐treated mice retained their capacity to reject a human acute myeloid leukemia cell line. Collectively, these data indicate for the first time that an antibody directed against CCR 7 might represent a viable new approach for aGVHD prevention.