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

Autor: Fowler KA; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina., Vasilieva V; MSM Protein Technologies, Waltham, Massachusetts., Ivanova E; MSM Protein Technologies, Waltham, Massachusetts., Rimkevich O; MSM Protein Technologies, Waltham, Massachusetts., Sokolov A; MSM Protein Technologies, Waltham, Massachusetts., Abbasova S; MSM Protein Technologies, Waltham, Massachusetts., Kim E; MSM Protein Technologies, Waltham, Massachusetts., Coghill JM; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.; Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Jazyk: angličtina
Zdroj: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons [Am J Transplant] 2019 Jul; Vol. 19 (7), pp. 1941-1954. Date of Electronic Publication: 2019 Mar 13.
DOI: 10.1111/ajt.15298
Abstrakt: 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 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 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 (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 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 CCR7 might represent a viable new approach for aGVHD prevention.
(© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)
Databáze: MEDLINE
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