In silico simulation of a clinical trial with anti-CTLA-4 and anti-PD-L1 immunotherapies in metastatic breast cancer using a systems pharmacology model.

ABSTRACT: The low response rate of immune checkpoint blockade in breast cancer has highlighted the need for predictive biomarkers to identify responders. While a number of clinical trials are ongoing, testing all possible combinations is not feasible. In this study, a quantitative systems pharmacology model is built to integrate immune-cancer cell interactions in patients with breast cancer, including central, peripheral, tumour-draining lymph node (TDLN) and tumour compartments. The model can describe the immune suppression and evasion in both TDLN and the tumour microenvironment due to checkpoint expression, and mimic the tumour response to checkpoint blockade therapy. We investigate the relationship between the tumour response to checkpoint blockade therapy and composite tumour burden, PD-L1 expr

SUBMITTER: Wang H 

PROVIDER: S-EPMC6549962 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature