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 (CCR7) is critical for aGVHD pathogenesis but dispensable for beneficial graft-versus-leukemia (GVL) responses. As a result, we evaluated a fully human anti-CCR7 blocking antibody as a new approach to prevent aGVHD in preclinical models. Here we report that antibody R707 is able to block human CCR7 signaling and function in vitro in response to its two 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 (PBMCs). R707 limited CD4+ and in particular CD8+ 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 anti-tumor potential of the PBMC inoculum as antibody-treated mice retained their capacity to reject a human AML cell line. Collectively, these data indicate for the first time that an antibody directed against CCR7 might represent a viable new approach for aGVHD prevention. This article is protected by copyright. All rights reserved.