One of the main challenges faced in cell therapies is the timely generation of a sufficient amount of high quality (functional) therapeutic cells for infusing into patients. Often, these three features of timely generation, sufficient amount and high quality engineered cells are not co-existent. For example, for autologous CAR-T cell therapy, often numbers in the hundreds of millions (10E8) to billions (10E9) of cells will be required for each infusion. Therefore, prolonged culture may be required to achieve sufficient cell production. However, during long-term culture, cells tend to undergo senescence, exhaustion and differentiation which result in loss of tumor-killing activities. Hence, a robust cell culture system capable of producing a clinical scale of genetically engineered cells without sacrificing its quality is needed.
GenomeFrontier Therapeutics, Inc. overcomes this challenge by introducing iCellar™ , which is a platform comprising proprietary agents and/or gene-modified cells that are designed to enhance cell expansion capacity while maintaining cell quality.
Upon antigen stimulation of naïve (TN) cells, cells will first differentiate into TSCM cells and may continue to differentiate into short-lived TEFF, the most differentiated and exhausted T cell. It has been clinically-proven that high amounts of CAR+ TSCM cells lead to better clinical response presumably due to its desired quality, namely greatest fitness and highest persistence as illustrated in Figure 1 .
For timely generation of clinical scale CAR-T cells that are highly-enriched in CAR+ TSCM cells , we have successfully developed iCellar™ system comprising two components: (1) Artificial antigen presenting cells (aAPC) that act to enrich and expand CAR+ T cells; and (2) Quantum Booster™ which acts to robustly expand TSCM cells. In combination, we show that these agents and cells (1) markedly enriched CAR+ T subpopulation; (2) with up to 90% of CD4+/CAR+ and CD8+/CAR+ being TSCM cells; and (3) increased expansion fold change of CAR-T cells while preserving their quality (Figure 2 ). Within ten days of culture, iCellar enables production of high CAR+ TSCM cell population in clinical scale (~10E9).
