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

Article

作者: Chen, Chen ; Yue, Xilian ; Suo, Bing ; Dong, Yuqi ; Zhou, Yang ; Han, Peng ; Qiao, Haiquan

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.

2021-01-01·Journal of Biological Chemistry2区 · 生物学

Effective delivery of STING agonist using exosomes suppresses tumor growth and enhances antitumor immunity

2区 · 生物学

Article

作者: Kathleen M. McAndrews ; Raghu Kalluri ; Sara P.Y. Che ; Valerie S. LeBleu

The Stimulator of Interferon Genes (STING) pathway is implicated in the innate immune response and is important in both oncogenesis and cancer treatment. Specifically, activation of the cytosolic DNA sensor STING in antigen-presenting cells (APCs) induces a type I interferon response and cytokine production that facilitates antitumor immune therapy. However, use of STING agonists (STINGa) as a cancer therapeutic has been limited by unfavorable pharmacological properties and targeting inefficiency due to rapid clearance and limited uptake into the cytosol. Exosomes, a class of extracellular vesicles shed by all cells are under consideration for their use as effective carriers of drugs owing to their innate ability to be taken up by cells and their biocompatibility for optimal drug biodistribution. Therefore, we engineered exosomes to deliver the STING agonist cyclic GMP-AMP (iExo^STINGa), to exploit their favorable pharmacokinetics and pharmacodynamics. Selective targeting of the STING pathway in APCs with iExo^STINGa was associated with superior potency compared with STINGa alone in suppressing B16F10 tumor growth. Moreover, iExo^STINGa showed superior uptake of STINGa into dendritic cells compared with STINGa alone, which led to increased accumulation of activated CD8⁺ T-cells and an antitumor immune response. Our study highlights the potential of exosomes in general, and iExo^STINGa specifically, in enhancing cancer therapy outcomes.

Frontiers in Immunology2区 · 医学

STING Agonist Combined to a Protein-Based Cancer Vaccine Potentiates Peripheral and Intra-Tumoral T Cell Immunity

2区 · 医学

ArticleOA

作者: Derouazi, Madiha ; Carboni, Susanna ; Di Berardino-Besson, Wilma ; Belnoue, Elodie ; Santiago-Raber, Marie-Laure ; Rossi, Matteo ; Riva, Erika

Combining different immunotherapy approaches is currently building the future of immunotherapy, with the view to maximize anti-tumoral efficacy for larger patient population. The KISIMA™ platform allows the development of protein-based cancer vaccines able to induce tumor-specific T cell response resulting in anti-tumoral efficacy in various mouse models. Intra-tumoral administration of stimulator of interferon gene agonists (STINGa) was shown to induce a potent inflammatory response leading to the development of tumor-specific immunity. Here, we explored the efficacy and mechanisms of action of subcutaneous STINGa treatment combined with therapeutic vaccination in various mouse tumor models. This combinatory treatment highly enhanced frequency and effector function of both peripheral and intra-tumoral antigen-specific CD8 T cells, promoting potent IFNγ and TNFα production along with increased cytotoxicity. Moreover, combination therapy favorably modulated the tumor microenvironment by dampening immune-suppressive cells and increasing CD4 T cell infiltration together with their polarization toward Th1 phenotype. Combination with STINGa treatment improved the effect of therapeutic vaccination, resulting in a prolonged control and slower growth of B16-OVA and TC-1 tumors. Altogether, the results presented here highlight the potential of combining STINGa with a therapeutic protein vaccine for cancer treatment.

100 项与 Star-STINGa 相关的药物交易

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