Periodic Reporting for period 1 - JetCell (Microfluidic bubble JET flow CELL sorter for cell therapy)
Reporting period: 2018-01-01 to 2019-06-30
Cell based cancer therapy has been recognized as one of the most promising new cancer treatments for the future. In particular, CAR-T cell therapies in which the patient’s own immune system is boosted to fight cancer is becoming popular with first clinical approved therapies reaching the market, and more than 262 start-ups in various stages of clinical studies. In a typical T cell therapy workflow, relevant T cells are isolated from the patient blood, modified to recognize certain cancer markers, infused back to the patient body where the engineered T cells direct the immune system to attack and finally eliminate the malignant tumor cells and tissues.
Recently, clinical researches discovered that purified T cell subsets could greatly improve therapeutic efficacy. However, currently T cell enrichment techniques including fluorescence activated cell sorting and immunomagnetic isolation are very expensive, too slow or do not reach sufficient purity. Therefore, it becomes difficult to deploy these methods at large scale. Consequently, there is a need for a safe, affordable and more precise single T cell sorting method for cell therapy applications.
In the original grant ERC-SCALPEL project, we developed a thermal vapor bubble jet flow technique for high speed fluorescence cell sorting. The bubble jet flow sorter was based on a precisely fabricated metal heater in a silicon chip. A short current pulse applied to this metal heater induces an array of micro vapor bubbles and consequently a jet flow for high speed aerosol-free single cell sorting at 5,000 cells/sec. The technique is intrinsically high throughput because each sorter can be replicated N times on chip to reach N times 5000 cells per second.
In this proof of concept project JETCELL, the bubble jet sorter has shown promise to serve the cell therapy demand: high precision combined with high throughput sorting, while the T cells remain viable and do not lose their potency for expansion. Moreover, the implementation as a closed system microfluidics enables high biosafety and affordability.
The JetCell project has completed a feasibility study of the bubble jet sorting technology for the enrichment of plain T helper steps as a first step of typical cell manufacturing for cancer cell therapy. With a prototype setup, the potential of the bubble jet sorter has been addressed in typical pre-clinical cell manufacturing models, from human cell lines to blood cells. The potential to select T cells with high purity and unaltered potency using a cell sorter device has been demonstrated, and compared to GMP compliant magnetic bead-based selection methods used currently in manufacturing.
Meanwhile, the cell therapy manufacturing market has been consulted, the competitive landscape has been analysed and the best product and business development strategy investigated.
Recently, clinical researches discovered that purified T cell subsets could greatly improve therapeutic efficacy. However, currently T cell enrichment techniques including fluorescence activated cell sorting and immunomagnetic isolation are very expensive, too slow or do not reach sufficient purity. Therefore, it becomes difficult to deploy these methods at large scale. Consequently, there is a need for a safe, affordable and more precise single T cell sorting method for cell therapy applications.
In the original grant ERC-SCALPEL project, we developed a thermal vapor bubble jet flow technique for high speed fluorescence cell sorting. The bubble jet flow sorter was based on a precisely fabricated metal heater in a silicon chip. A short current pulse applied to this metal heater induces an array of micro vapor bubbles and consequently a jet flow for high speed aerosol-free single cell sorting at 5,000 cells/sec. The technique is intrinsically high throughput because each sorter can be replicated N times on chip to reach N times 5000 cells per second.
In this proof of concept project JETCELL, the bubble jet sorter has shown promise to serve the cell therapy demand: high precision combined with high throughput sorting, while the T cells remain viable and do not lose their potency for expansion. Moreover, the implementation as a closed system microfluidics enables high biosafety and affordability.
The JetCell project has completed a feasibility study of the bubble jet sorting technology for the enrichment of plain T helper steps as a first step of typical cell manufacturing for cancer cell therapy. With a prototype setup, the potential of the bubble jet sorter has been addressed in typical pre-clinical cell manufacturing models, from human cell lines to blood cells. The potential to select T cells with high purity and unaltered potency using a cell sorter device has been demonstrated, and compared to GMP compliant magnetic bead-based selection methods used currently in manufacturing.
Meanwhile, the cell therapy manufacturing market has been consulted, the competitive landscape has been analysed and the best product and business development strategy investigated.