Unknown

Dataset Information

0

Increased frequency of ICOS+ CD4 T cells as a pharmacodynamic biomarker for anti-CTLA-4 therapy.


ABSTRACT: Pharmacodynamic biomarkers can play an important role in understanding whether a therapeutic agent has "hit its target" to impact biologic function. A pharmacodynamic biomarker for anti-CTLA-4 therapy remains to be elucidated. We previously reported that anti-CTLA-4 therapy increases the frequency of CD4 T cells expressing the inducible costimulator (ICOS) molecule. To determine whether the frequency of ICOS(+) CD4 T cells could be used as a pharmacodynamic biomarker for anti-CTLA-4 therapy, we carried out flow cytometric studies and statistical analyses on data from 56 individuals, which included 10 healthy donors, 36 patients who received anti-CTLA-4 monoclonal antibody (mAb), and 10 patients who received treatment with a different immunomodulatory agent (gp100 DNA vaccine). After treatment with anti-CTLA-4 mAb (ipilimumab; Bristol-Myers Squibb), we detected a statistically significant increase in the frequency of ICOS(+) CD4 T-cells. After two doses of anti-CTLA-4 therapy, the assay was found to have an estimated specificity of 96% [95% confidence interval (CI), 88-100] and sensitivity of 71% (95% CI, 54-85), with positive expression defined as a frequency that is more than the upper bound of 95% CI among baseline samples from all subjects. Our data suggest that an increased frequency of ICOS(+) CD4 T cells measured by flow cytometry can be used as a reproducible pharmacodynamic biomarker to indicate biologic activity in the setting of anti-CTLA-4 therapy, which should enable appropriate immune monitoring to determine whether patients receiving anti-CTLA-4 monotherapy or combination treatment strategies are having an adequate biologic response.

SUBMITTER: Ng Tang D 

PROVIDER: S-EPMC4636341 | BioStudies | 2013-01-01

REPOSITORIES: biostudies

Similar Datasets

2014-01-01 | S-EPMC4004958 | BioStudies
1000-01-01 | S-EPMC2650334 | BioStudies
2009-01-01 | S-EPMC2917097 | BioStudies
2010-01-01 | S-EPMC2919850 | BioStudies
2016-01-01 | S-EPMC4800751 | BioStudies
2019-01-01 | S-EPMC6527285 | BioStudies
2020-01-01 | S-EPMC7762776 | BioStudies
2014-01-01 | S-EPMC4077286 | BioStudies
2017-01-01 | S-EPMC5296272 | BioStudies
2019-01-01 | S-EPMC6838990 | BioStudies