Beta glucan immunopharmacodynamics

Abstract

This disclosure provides, in one aspect, dosing strategies for soluble β-glucan immunotherapy to optimize acute immunopharmacodynamic responses for the immunotherapy and/or subject. It also provides a method for analyzing a sample from a subject for a biomarker to identify the appropriate dosing strategy for soluble β-glucan immunotherapy. Generally, the method includes obtaining a biological sample from a subject, analyzing the sample for a biomarker anti-β-glucan antibody level or immunopharmacodynamic response level, classifying the subject into a subgroup based on the biomarker anti-β-glucan antibody level or immunopharmacodynamic response level and identifying the appropriate dosing strategy based on the subgroup classification.

What is claimed is: 
     
         1 . A method comprising:
 obtaining a biological sample from a subject;   analyzing the sample for a biomarker anti-β-glucan antibody level;   classifying the subject into a subgroup based on the biomarker anti-β-glucan antibody level; and   identifying an appropriate dose strategy of soluble β-glucan for the subject based on the subject's subgroup.   
     
     
         2 . A method comprising:
 obtaining a biological sample from a subject;   analyzing the sample for an immunopharmacodynamic response level; and   classifying the subject into a subgroup based on the immunopharmacodynamic response level; and   identifying an appropriate dose strategy of soluble β-glucan for the subject based on the subject's subgroup.   
     
     
         3 . The method of  claim 1  wherein the biomarker anti-β-glucan antibody comprises IgG. 
     
     
         4 . The method of  claim 2  wherein the immunopharmacodynamic response comprises anti-β-glucan antibody levels, circulating immune complex levels, complement activity levels, cytokine/chemokine production levels, levels of immune cell binding, mobilization of immune cells and expression levels of innate immune activation marker genes. 
     
     
         5 . The method of  claim 1  or  3  wherein classification includes 2 to 5 subgroups. 
     
     
         6 . The method of  claim 1  or  3  wherein the dosing strategy includes pre-dosing the subject 1 or more times with soluble β-glucan. 
     
     
         7 . The method of  claim 1  wherein the classifying subgroups include a low-level anti-β-glucan antibody subgroup, a mid-level anti-β-glucan antibody subgroup and a high-level anti-β-glucan antibody subgroup. 
     
     
         8 . The method of  claim 7  wherein the appropriate dose of soluble β-glucan for the low-level anti-β-glucan antibody subgroup and the mid-level anti-β-glucan antibody subgroup is higher than the appropriate dose of soluble β-glucan for the high-level anti-β-glucan antibody subgroup. 
     
     
         9 . The method of any preceding claim wherein the β-glucan is derived from yeast. 
     
     
         10 . The method of any preceding claim wherein the β-glucan comprises a β-1,3/1,6 glucan. 
     
     
         11 . The method of any preceding claim wherein the β-glucan comprises β(1,6)-[poly-(1,3)-D-glucopyranosyl]-poly-β(1,3)-D-glucopyranose. 
     
     
         12 . A method comprising:
 administering multiple doses of soluble β-glucan to a subject over a course of immunotherapy treatment, wherein the time interval between administration of each dose optimizes acute immunopharmacodynamic responses for the immunotherapy treatment.   
     
     
         13 . The method of  claim 12  wherein the time interval ranges from 2 weeks to 12 weeks. 
     
     
         14 . The method of  claim 12  wherein the time internal ranges from 8 days to 84 days. 
     
     
         15 . The method of  claim 12  wherein immunopharmacodynamic responses and/or anti-β-glucan antibody level of the subject are analyzed to determine the optimal time interval. 
     
     
         16 . A method comprising:
 administering a single dose of soluble β-glucan to a subject over a course of immunotherapy treatment.