SYK inhibitor entospletinib prevents ocular and skin GVHD in mice.

Published

Journal Article

Graft-versus-host disease (GVHD) is a major complication of hematopoietic stem cell transplantation (HCT). The tyrosine kinase SYK contributes to both acute and chronic GVHD development, making it an attractive target for GVHD prevention. Entospletinib (ENTO) is a second-generation highly selective SYK inhibitor with a high safety profile. Potential utility of ENTO as GVHD prophylaxis in patients was examined using a preclinical mouse model of eye and skin GVHD and ENTO-compounded chow. We found that early SYK inhibition improved blood immune cell reconstitution in GVHD mice and prolonged survival, with 60% of mice surviving to day +120 compared with 10% of mice treated with placebo. Compared with mice receiving placebo, mice receiving ENTO had dramatic improvements in clinical eye scores, alopecia scores, and skin scores. Infiltrating SYK+ cells expressing B220 or F4/80, resembling SYK+ cells found in lichenoid skin lesions of chronic GVHD patients, were abundant in the skin of placebo mice but were rare in ENTO-treated mice. Thus, ENTO given early after HCT safely prevented GVHD.

Full Text

Duke Authors

Cited Authors

  • Poe, JC; Jia, W; Di Paolo, JA; Reyes, NJ; Kim, JY; Su, H; Sundy, JS; Cardones, AR; Perez, VL; Chen, BJ; Chao, NJ; Cardona, DM; Saban, DR; Sarantopoulos, S

Published Date

  • October 4, 2018

Published In

Volume / Issue

  • 3 / 19

PubMed ID

  • 30282825

Pubmed Central ID

  • 30282825

Electronic International Standard Serial Number (EISSN)

  • 2379-3708

International Standard Serial Number (ISSN)

  • 2379-3708

Digital Object Identifier (DOI)

  • 10.1172/jci.insight.122430

Language

  • eng