iCellar™
Molecular and cellular reagents to promote expansion of high-quality therapeutic cells
A major challenge in cell therapy manufacturing is the efficient generation of high-quality therapeutic cells at sufficient numbers. Since cell numbers on the order of 10⁸ or 10⁹ are often required for a single infusion of an autologous CAR T cell therapy, the genetically modified cells often need to be expanded for extended times. During prolonged cell expansion steps, cells tend to adopt senescent, exhausted and differentiated phenotypes, which are undesirable for therapeutic cells. To overcome this challenge, GenomeFrontier has developed iCellar™. This platform is built from proprietary molecular reagents and gene-modified antigen-presenting cells that can be used to enhance cell expansion capacity while maintaining high-quality cellular phenotypes.
Early differentiation stage T cells (TN/TSCM) are the most desirable subtypes for CAR T cell therapies, as CAR T cells with higher levels of these subsets are consistently more efficacious and safer. In contrast, the expression of exhaustion and senescence markers is negatively associated with efficacy and safety of CAR T cells. CAR⁺ TSCM cells likely lead to better clinical outcomes due to their high metabolic fitness, stemness, and long-term persistence.
Figure 1. Naïve T (TN) cells expand and differentiate upon antigen stimulation. Following the activation of TN cells by encountering antigen presenting cells (APCs), long-lived TSCM and TCM cells are produced. These self-renewing T cell populations give rise to expanded populations of shorter-lived TEM and TEFF cells. TSCM cells are thought to be the most therapeutically efficacious T cell population.
The iCellar™ platform comprises (1) artificial antigen presenting cells (aAPCs) to enrich and expand CAR⁺ T cells; and (2) Quantum Booster™ to enrich TSCM cells. Combining these two reagents markedly increases the percentage of CAR⁺ T cells. Expansion with iCellar™ can yield up to 90% TSCM cells among CD4⁺ CAR⁺ and CD8⁺ CAR⁺ populations. Notably, the increased expansion of CAR T cells does not come at the expense of cell quality. Most importantly, iCellar™ enables production of high-quality CAR⁺ TSCM cells at a clinical scale (1×10⁹ CAR+ cells) in a 10-day expansion period.
