Fluorophore-Conjugated Anti-ICOS Antibody Enables Precise Prediction of Therapeutic Response of the STING Agonist in Colorectal Cancer via NIRF Imaging.

Abstract

The innovation of cancer immunotherapy is improving the prognosis of colorectal cancer (CRC) in clinics. Nevertheless, due to tumor heterogeneity and complex underlying inhibitory mechanisms, the therapeutic response greatly varies among different patients. To optimize the clinical management of CRC patients, it is critical to develop novel approaches for response monitoring and prediction. In the current study, we developed a novel near-infrared fluorescence (NIRF) imaging probe (Cy5.5-ICOS mAb) targeting the inducible T-cell costimulatory receptor (ICOS or CD278) and assessed its capacity for the detection of ICOS+-activated T cells in vivo. ICOS expression was evaluated by flow cytometry and immunofluorescence staining in subcutaneous MC38 models treated with the stimulator of interferon genes (STING) agonist (STINGa). NIRF imaging study was performed 1 day after the last treatment, and tumor volume was monitored every other day with a caliper. A significantly higher optical signal could be detected at tumor regions in STINGa group, compared with that in the PBS group at all time points imaged, and this was in line with ex vivo imaging and immunofluorescence staining study. The data demonstrated that Cy5.5-ICOS mAb could detect ICOS+-activated T cells with high specificity, and ICOS NIRF imaging is a promising strategy for predicting and monitoring immune response in CRC.