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SLAS Cambridge 2023
This year’s conference and exhibition will feature four important tracks focused on life sciences and their global impact: Biology Unveiled, Frontiers in Technology, Shaping the Future of Therapeutics and Bio-Entrepreneurship in Europe.
Will you be there too?
Head to our exhibition stand – #324
Our dedicated team of creative problem solvers will be available to answer questions and share over a decade of organ-on-a-chip (OOC) expertise with you!
We look forward to meeting you to discuss how our PhysioMimix™ suite of hardware, consumables, assay protocols and services can help to improve the predictivity of your drug discovery workflows and address workflow limitations – such as modeling the immune system in vitro and testing the safety of new modality drugs with human specific modes of action.
Get familiar with our predictive human models and learn more about their proven track record for delivering clinically translatable results, plus meet the new game-changing product in our PhysioMimix OOC range of microphysiological systems, the PhysioMimix Single-organ Higher Throughput (HT) System and associated Multi-chip Liver-48 plate.
A microphysiological platform to translate PK/PD profiles and to explore anti-cancer therapies efficacy on 3D tumour spheroids and patient derived organoids.
TBC..
Anticancer scheduled therapies should display maximized efficacy combined with minimal side effects. To accomplish this endeavour, an accurate understanding of the pharmacokinetic/pharmacodynamic (PK/PD) relationship of the compound(s) is required (1). Most static or microfluidic in vitro experiments are mainly performed at fixed concentrations and do not explore PK/PD relationships, thus limiting their translational relevance (2).
Aiming to explore human tumour-specific responses to known and novel anticancer therapies, we have developed a microphysiological system (MPS) able to mimic human PK/PD efficacy relationships. Our platform is able to explore efficacy of mono or combination therapy (on various therapeutic schedules) on 3D tumour spheroid models and patient derived organoids.
We initially recapitulated the in vivo PK/PD relationship for a PI3K inhibitor (BYL719- t1/2 = 6 hours, equivalent to 50 mg/kg murine oral dose), used to treat an A549 non-small cell lung carcinoma model. Following BYL719 exposure in the MPS platform, cellular p-AKT levels (biomarker of PI3K pathway activity) fell by up to 50%, and then recovered to pre-dosed levels over a 24-hour period, for 3 days in a row. This effect is not captured in standard in vitro bolus experiments.
Right after, we explored whether the MPS could recapitulate in vivo effects of combining topoisomerase inhibitors with DNA-damage-response inhibitors (DDRi) in the treatment of 3D colorectal tumour models – spheroids and multiple donor patient-derived organoids. We mimicked the murine PK profiles for 6 days with the delivery of mono and combination therapies (SN38 Cmax = 20 nM, DDRi Cmax = 162 nM. Viability assays and fluorescent labelled biomarker expression evaluated by confocal microscopy demonstrated the benefits of combination therapy, with efficacy rates consistent with in vivo observations, in contrast to static 2D in vitro cultures.
Our MPS platform is able to mimic animal and human PK profiles thus potentially avoiding many failures of novel therapies which are due to a missing physiologically relevant link between preclinical and clinical data. By tailoring individualized PK profiles and therapeutic schedules, we introduce a valuable tool and strategy in the pursuit of personalized medicine for the treatment of cancer.
[1] Malik et al (2021) doi.org/10.3389/fcell.2021.721338
[2] Sonhheimer-Phelps et al (2019) doi: 10.1038/s41568-018-0104-6
Presenter: Dr Tudor Petreus,
CN Bio
Our Team at AASLD
Adrian
A seasoned business developer with extensive commercial experience in the life science sector, Adrian Rea joined CN-Bio Innovations as the European Director of Sales in June 2022. He brings valuable experience in the 3D cell culture market from his most recent role at InSphero, where he was responsible for developing business opportunities in European and Asian markets. He was previously Sales Director at Enzo Life Sciences, where he managed the restructuring of the global distributor sales channels and expanding the European sales operations. Adrian graduated from the University of Glasgow and received his PhD in pharmacology from Glasgow Caledonian University.
Atefeh
Dr Atefeh Mobasseri, Field Application Scientist at CN Bio, has an extensive background in tissue engineering and regenerative medicine. Before joining CN Bio, she gained a PhD in Biomedical materials from the University of Manchester and carried out postdoctoral roles at the University of Manchester and Kings College London investigating the interaction, and effect, of 3D scaffolds on cellular behaviour. Since joining CN Bio, she has been supporting their European customers in using CN Bio’s range of PhysioMimixTM systems to generate high content, human-relevant, data.
Parham
Dr Parham Ashrafzadeh is the UK/Nordics Account Manager at CN Bio and is based in London. Parham helps scientists within academia, biotech and pharma sectors to find the best solutions for testing their therapeutics which are more cost-effective, clinically relevant and safer at the drug discovery stage. Parham holds a PhD from Uppsala University in Sweden and completed a collaborative postdoctoral fellowship between four universities around the globe.