FluoScore

Systemic drug platform

Bringing Clarity from Shadows:

FluoScore bridges the gap between lab and clinic by integrating safety and efficacy testing in human systems that mirrors real organ interactions.

Multiplexed co-culture of healthy and disease tissue models to simultaneously measure drug safety and efficacy in the presence of drug-metabolizing tissues.

Reliable prediction of drug effects by reaching human and systemic relevance with multi-tissue systems mimicking communications between organs (metabolic, hormonal, immunological).

High assay flexibility to test drugs on different tissues combinations, allowing precise insights and integrated view of key pharmacological interactions.

Integrated Drug
Evaluation

Drug safety, efficacy, and metabolization assessed with multi-tissue systems

Drug
Systemic Activity

Capture complex interactions between organs influencing drug activity

High Assay
Flexibility

Multiple combinations for reliable prediction of drug pharmacology

Application

Prediction of Drug Systemic Effects

Systemic Efficacy

Integrated Toxicity/Efficacy Selectivity/Drug Metabolization

Systemic Toxicity

Systemic Interstitial Lung Disease (Collaboration Epithelix)

Workflow

Stages of production

Tissue
Compartmentalization

tissue A

Tissue b

tissue c

Tissue
Color-Coding

Multi-Tissue
Communications

drugs treatment

systemic communications

Effects
assessement

probe 1

probe 2

Multi 
Detection

effect 1

effect 2

Case study: Results

Tamoxifen: Liver-dependent efficacy on breast adenocarcinoma

About the drug

Tamoxifen is the first endocrine therapy drug and one of the most prescribed to treat breast cancer since more than four decades. However, Tamoxifen was discovered fortuitously because it is inactive by itself. Indeed, it needs to be metabolized by the liver first to be active against breast tumors (Figure 1). The liver-dependent efficacy of Tamoxifen on breast adenocarcinoma has never been demonstrated in vitro because of the lack of systemic assay available.

Experimental design

To evaluate the liver-dependent efficacy of Tamoxifen, we designed a 2-tissue co-culture with encapsulated liver spheroids (HepaRG cell line) and encapsulated breast cancer spheroids (MCF-7 cell line) expressing a reporter gene to measure the activity of the estrogen receptor, the target of Tamoxifen. A dose-response with increasing doses of Tamoxifen was performed on the co-culture and on a mono-culture of encapsulated breast cancer spheroids and the estrogen response was measured after 48h of treatment. A mass spectrometry analysis was carried out in parallel to analyze the effective metabolization of Tamoxifen by liver spheroids.

Figure

Figure 1: Metabolization of Tamoxifen by the liver with the enzymes involved and the different metabolic byproducts.

Figure 2: Dose-response of Tamoxifen on the estrogen receptor activity in breast cancer spheroids co-cultured or not with liver spheroids.

Figure 3: Mass spectrometry analysis of cell culture supernatants from liver spheroids treated with Tamoxifen

Key Results

Strong activation (>5-fold) of the antiestrogen activity of Tamoxifen in breast cancer spheroids by liver spheroids (Figure 2).
Metabolization of Tamoxifen into its active metabolite, 4-hydroxytamoxifen, by liver spheroids (Figure 3).

References

V Craig Jordan. Tamoxifen: a most unlikely pioneering medicine. Nature Reviews Drug Discovery, 2: 205-213 (2003).
Saladores P, Mürdter T, Eccles D.Tamoxifen metabolism predicts drug concentrations and outcome in premenopausal patients with early breast cancer. Pharmacogenomics Journal 15: 84–94 (2015).
Dai X, Cheng H, Bai Z, Li J, et al. Breast Cancer Cell Line Classification and Its Relevance with Breast Tumor Subtyping. Journal of Cancer, 8(16): 3131-3141 (2017).

Case study: Results

Irinotecan: Liver-dependent efficacy on colon carcinoma, hepatotoxicity, and selectivity (colon cancer vs breast cancer)

About the drug

Irinotecan is an anticancer drug mainly used as a first-line therapy for colorectal cancer. Irinotecan has a second therapeutic indication which is the small cell lung carcinoma, but it is less active on other types of cancer. It is activated by the liver and by plasmatic enzymes into SN-38, the active metabolite of Irinotecan. Then, SN-38 is transported to colon carcinoma cells to exert its antineoplasic activity.

Experimental design

To assess simultaneously the liver-dependent efficacy of Irinotecan and its selectivity, we designed a 3-tissue co-culture system consisting of encapsulated liver spheroids (HepaRG), colon carcinoma spheroids (HCT-116), and breast adenocarcinoma spheroids (MCF-7), treated with increasing doses of Irinotecan for 48h. A staining with AnnexinV-FITC was performed to quantify the induction of apoptosis (cytotoxicity) of Irinotecan. The colors of the capsules were used to independently and simultaneously measured the effect of Irinotecan in the three tissue types. A mono-culture of each type of tissue and a co-culture without the liver tissue were made in parallel to evaluate the activation of Irinotecan by the liver.

Figure

Figure 1: Metabolization of Irinotecan by the liver with the enzymes involved and the active metabolite.

Figure 2: Confocal images with Colon/Breast cancer co-cultures with (left) or without Liver spheroids (right), treated 48h with Irinotecan 10µM. The induction of apoptosis was measured with an AnnexinV-FITC staining.

Figure 3: Cytotoxicity of increasing doses of Irinotecan on liver, colon, and breast cancer spheroids in mono- or tri-culture, quantified by measuring the AnnexinV signal expressed as fold of control.

Key Results

Potentialization of the efficacy of Irinotecan (2-fold increase) on colon carcinoma spheroids by liver spheroids.
Dose-dependent hepatotoxicity of Irinotecan.
Selective efficacy: no effect on breast adenocarcinoma spheroids.

References

Fuchs C, Mitchell EP, Hoff PM. Irinotecan in the treatment of colorectal cancer. Cancer Treatment Reviews, 32(7): 491-503 (2006).
Mathijssen RHJ, van Alphen RJ, Verweij J, et al. Clinical Pharmacokinetics and Metabolism of Irinotecan (CPT-11). Clinical Cancer Research, 7(8): 2182–2194 (2001).

News

Articles & Resources

June 11, 2024

FluoSphera and Revvity Collaborate to Develop a Multiplexed Selectivity Assay for In Vitro Drug Discovery

Read Article

FluoSphera's technology is a multi-organoid system that combines encapsulated tissues to mimic the complex human system, enabling reliable in vitro drug discovery.

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