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INV13

Industrial production of cultured red blood cells: a model for future large-scale cell therapies finally within reach

G F Rousseau ¹, L Douay ¹ ²

1: Erypharm    2: Sorbonne Université, Paris

Despite continuous progresses, current leading-edge technologies do not allow for affordable production of large-scale cell therapies requiring vast numbers of cells, such as certain regenerative cell therapies, allogeneic CAR-T cell approaches and cultured red blood cells (cRBC). The development of cRBC undoubtedly represents the greatest industrial challenge facing these applications due to the very large volume of clinical doses (>10¹² cells). Hence, scientific and technological barriers must be overcome in terms of yield and production costs to transform these visions into tangible realities.

Strikingly, the potential clinical value of stem cell-derived cRBC in blood transfusion has already been established on a small scale, offering exciting prospects for transfusion-dependent patients. However, estimated production costs with standard processes are prohibitive. Industrial scale-up and economic sustainability will require a drastically intensified process. Cell culture media represent the bulk of manufacturing costs, with proteins (albumin, growth factors etc.) being the main cost drivers. Reducing, replacing or recycling proteins is therefore the key objective.

We embraced these challenges to develop ERYCULT™, a scalable technology inspired by perfusion, achieving more than 20-fold cell concentration (100x10⁶ cells/mL) vs. conventional batch, while simultaneously preserving 95% of proteins, which allows a > 25-fold reduction of production costs.

Successfully developed on a scale of 2 L, ERYCULT™ already yields 1/10th of a cRBC unit per batch. Our technology thus offers a ground-breaking solution for the industrial production of cRBC, together with other similar large-scale cell therapies, and could lead to a new era in transfusion.

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