Graft vs Host Disease (GVHD): Preclinical Efficacy Services

JAX works with you to design studies that
yield clinically relevant results.

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Benefits of Services at JAX

  • Project support from Ph.D.-level study directors from initial study design to reporting
  • Extensive experience conducting large-scale GvHD studies for commercial clients
  • Outcomes compared to a clinically-approved immunosuppressive drug (e.g., etanercept)
  • Industry leading PBMC-humanized-NSG™ mice

Industry-Leading Hu-PBMC-NSG™

Humanized-PBMC-NSG™ mice are widely used as models of human-to-mouse xenogeneic GvHD, as well as studying immune function in vivo. Peripheral blood mononuclear cells (PBMCs) engraft with high efficiency into NSG™ mice due to the lack of mature murine lymphocytes and natural killer cells. The high degree of immunodeficiency allows engraftment of larger cohorts from a single donor, creating a robust and reproducible study platform.

GvHD Study Design

Standard study includes: 

  • Midpoint and terminal blood samples
  • Survival curves
  • Study report
  • Body Scoring Scale and Clinical Observation (BCS)

Optional Add-Ons:

  • FACS analysis of blood and spleen
  • Blood cytokine analysis
  • Tissue collection and histopathology
  • Additional treatment arms
  • Alternative benchmarking agent available
 

Example Study

Shown in the figure below are sample control and vehicle arms of a standard five arm study.  Survival (A) and body weight (B) data demonstrate efficacy of the immunosuppressive drug Enbrel® (etanercept) in this platform. Standard studies run for thirty-five days and include dosing up to three times weekly for five weeks. Assessments are performed three times per week. A quality control group is engrafted in parallel with study arms to confirm PBMC engraftment.

 GvHD

Sample data from preclinical GvHD study. A. Survival curve of saline-treated control (group 1) vs treatment with Enbrel® (etanercept, group 2). B. Mean body weight of untreated control group declines significantly more rapidly than treatment group (n = 20 or 12 per group).

Note: Disease Activity Index scoring is used to closely monitor animal health according to strict guidelines and approval by the Animal Care and Use Committee.

Contact us to discuss your study by clicking “Request a Quote” above or calling us at 1-800-422-6423.

Selected References

Ali N; Flutter B; Sanchez Rodriguez R; Sharif-Paghaleh E; Barber LD; Lombardi G; Nestle FO. 2012. Xenogeneic Graft-versus-Host-Disease in NOD-scid IL-2Rγ(null) Mice Display a T-Effector Memory Phenotype. PLoS One 7(8):e44219.  [PubMed: 22937164]

Norelli M, Camisa B, Bondanza A. 2016. Modeling Human Graft-Versus-Host Disease in Immunocompromised Mice. Methods Mol Biol. 2016; 1393:127-32. [PubMed: 27033222]

King M et al. 2008. Clin Immunol 126(3):303-14. PMID:18096436

King M et al. 2009. Clin Exp Immunol Jul;157(1):104-18. PubMed: 19659776

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Humanized Mice

NSG™ and NSG™-SGM3 Mice engrafted with human hematopoetic stem cells represent powerful tools for studying oncology, infectious disease, and hematopoiesis and are helping accelerate the development of novel therapies.

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New Blog Post: aPC- A New Strategy to Prevent Graft-vs-Host Disease (GvHD)

Investigating the thrombomodulin-aPC axis to treat or prevent GvHD.

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Whitepaper: Humanized Mice for Immuno-Oncology

NSG™ mice are a proven host for engraftment of human tumors or establishment of human immunity following hematopoietic stem cell transplantation.

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