Automated Cellular Cytotoxicity Assays with Autolus

Automate the setup of complex cytotoxicity assays easily, rapidly, and with the flexibility required for therapy development

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The Synthetic Genomics research group at Autolus started working with Synthace in 2019 as it recognized the need to improve the flexibility, robustness, and efficiency of its routine CAR T-cell cytotoxicity assays. The group was looking towards automation solutions that could provide a rapid and scalable approach to physical execution in the lab, which led them to adopt Synthace’s software platform.

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Gene-modified cell therapies

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In cell therapies, intact live cells are infused into a patient to elicit a therapeutic effect. In gene-modified cell therapies, cells are genetically modified prior to infusion: they are harvested from a patient (autologous therapy) or a healthy donor (allogeneic therapy), genetic material is inserted into them (often via a viral vector), they then undergo an expansion phase and are prepared for delivery back to the patient.

To date, three ex vivo autologous therapies have reached the market: Kymriah, Yescarta (CAR T-cell therapies), and Strimvelis (gene-modified haematopoietic stem cell therapy). At the start of 2020, gene-modified cell therapies were enrolled in 452 clinical trials, constituting 42% of all ongoing clinical trials in the regenerative medicine sector, which received the total global financing of $9.8 billion in 2019 [1].

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Key findings
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  • Synthace enabled Autolus scientists to rapidly and flexibly set up complex CAR T-cell cytotoxicity assays via liquid handling automation, using the Gilson PIPETMAX® liquid handler

  • Three different CAR-transduced effector cells significantly impaired target tumour cell growth, while next generation CARs were effective at bypassing inhibitory cytokine signalling

  • Synthace-driven automated liquid handling of mammalian cells maintained cell viability and transfer accuracy to the same level as manual pipetting, without compromising the results

  • Synthace provided remarkable pipetting consistency, with CV of 3.66% compared to 23.17% in manual execution
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