Back to results
US 11,959,926 B2Granted
Method of determining toxicity of an immunomodulatory drug for use in humans preliminary class
AssigneeThe Jackson Laboratory
InventorsJames Keck, Chunting Ye
Life of this patent
Estimating the term…
Abstract
Humanized mouse models and methods are provided for determining whether administration of an immunomodulatory drug likely elicits a severe cytokine release syndrome in a human. Humanized mouse models and methods are also provided for determining the immunotoxicity in a human of a drug candidate or of drug combinations.
Claims20
A method for assessing immune toxicity of an immunomodulatory agent on a human immune system, the method comprising:
- (a) administering human peripheral blood mononuclear cells (PBMCs) to an immunodeficient mouse that has been subjected to myeloablation;
- (b) administering an immunomodulatory agent to the immunodeficient mouse;
- (d) measuring blood concentration of a human cytokine selected from interferon-gamma (IFN-γ), interleukin (IL)-10, IL-6, IL-2, IL-4, and tumor necrosis factor alpha (TNFα) in a sample from the immunodeficient mouse before the immunodeficient mouse develops a symptom of graft versus host disease (GVHD);
- (e) determining severity of cytokine release induced by the immunomodulatory agent based on a comparison of the blood concentration of the human cytokine to a threshold value;
- and
- (f) assessing immune toxicity of the immunomodulatory agent on the human immune system based on the severity of cytokine release.
3 more elements
A method for assessing immune toxicity of an immunomodulatory agent on a human immune system, the method comprising:
- (a) administering human peripheral blood mononuclear cells (PBMCs) to an immunodeficient mouse that has been irradiated;
- (b) administering an immunomodulatory agent to the immunodeficient mouse fewer than 8 days after the administering human PBMCs;
- (c) measuring blood concentration of a human cytokine selected from interferon-gamma (IFN-γ), interleukin (IL)-10, IL-6, IL-2, IL-4, and tumor necrosis factor alpha (TNFα) in a sample from the immunodeficient mouse before the mouse develops a symptom of graft versus host disease (GVHD), wherein the symptom of GVHD is significant weight loss;
- (d) determining severity of cytokine release induced by the immunomodulatory agent based on a comparison of the blood concentration of the human cytokine to a threshold value;
- and
- (e) assessing immune toxicity of the immunomodulatory agent on the human immune system based on the severity of cytokine release.
3 more elements
Dependencies are inferred from the claim text.