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SYK inhibitor entospletinib prevents ocular and skin GVHD in mice.

Publication ,  Journal Article
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 ...
Published in: JCI Insight
October 4, 2018

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.

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Published In

JCI Insight

DOI

EISSN

2379-3708

Publication Date

October 4, 2018

Volume

3

Issue

19

Location

United States

Related Subject Headings

  • Treatment Outcome
  • T-Lymphocytes
  • Syk Kinase
  • Survival Analysis
  • Skin
  • Pyrazines
  • Protein Kinase Inhibitors
  • Mice
  • Indazoles
  • Humans
 

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Poe, J. C., Jia, W., Di Paolo, J. A., Reyes, N. J., Kim, J. Y., Su, H., … Sarantopoulos, S. (2018). SYK inhibitor entospletinib prevents ocular and skin GVHD in mice. JCI Insight, 3(19). https://doi.org/10.1172/jci.insight.122430
Poe, Jonathan C., Wei Jia, Julie A. Di Paolo, Nancy J. Reyes, Ji Yun Kim, Hsuan Su, John S. Sundy, et al. “SYK inhibitor entospletinib prevents ocular and skin GVHD in mice.JCI Insight 3, no. 19 (October 4, 2018). https://doi.org/10.1172/jci.insight.122430.
Poe JC, Jia W, Di Paolo JA, Reyes NJ, Kim JY, Su H, et al. SYK inhibitor entospletinib prevents ocular and skin GVHD in mice. JCI Insight. 2018 Oct 4;3(19).
Poe, Jonathan C., et al. “SYK inhibitor entospletinib prevents ocular and skin GVHD in mice.JCI Insight, vol. 3, no. 19, Oct. 2018. Pubmed, doi:10.1172/jci.insight.122430.
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. SYK inhibitor entospletinib prevents ocular and skin GVHD in mice. JCI Insight. 2018 Oct 4;3(19).

Published In

JCI Insight

DOI

EISSN

2379-3708

Publication Date

October 4, 2018

Volume

3

Issue

19

Location

United States

Related Subject Headings

  • Treatment Outcome
  • T-Lymphocytes
  • Syk Kinase
  • Survival Analysis
  • Skin
  • Pyrazines
  • Protein Kinase Inhibitors
  • Mice
  • Indazoles
  • Humans