Century Therapeutics Presents New Preclinical Data Highlighting iPSC-derived Cell Therapy Platform Technology at the 2024 American Association for Cancer Research (AACR) Annual Meeting - Seite 2

Engineered Expression Of HLA-E And HLA-G Protects iPSC-Derived Cells from Killing by Primary NK Cells
Poster Board Number: 3
Session Title: CAR-K, NK Engagers, and NK Modulators
Session Date & Time: Monday, April 8, 2024, at 9:00 AM - 12:30 PM PT

In this study, the Company showed that the combination of HLA-E and HLA-G expression was the most effective in protecting allogeneic drug products from elimination of genetically dissimilar cells. Investigators assessed allo-evasion from natural killer (NK) cells by iPSC-derived cells engineered to express HLA-E and -G. NK cells across donors expressed heterogeneous combinations of HLA-E and -G ligands. K562 and iPSC-derived cells lacking HLA-I were susceptible to killing by PBMCs. Overexpression of HLA-E and -G offered protection to K562 and iPSC-derived cells against all tested donors. HLA-E offered more protection than HLA-G, and the combination of both HLA-E and -G was most potent. When a genetically dissimilar HLA Class I protein family is deleted to prevent T cell mediated graft rejection, expression of the more-conserved HLA-E and -G can effectively protect allogeneic drug products from elimination. We believe this data further reinforces the Company’s proprietary Allo-Evasion technology and its potential to evade identification by the host immune system, which would allow for repeat dosing without rejection, enabling increased persistence of the cells during the treatment period and potentially leading to deeper and more durable responses.

Screening iPSC Lines for Optimal Characteristics of Differentiation into Immune Effector Cells for Clinical Programs
Poster Board Number: 19
Session Title: Adoptive Cellular Therapy 1
Session Date & Time: Monday, April 8, 2024, at 1:30 PM - 5:00 PM PT

Century outlined the genomic characterization of both its clinical-grade PBMC-derived and its gamma-delta T cell-derived iPSC lines (PiPSCs and TiPSCs, respectively). The Company successfully reprogrammed these cell lines from multiple donors and analyzed them through its genomic characterization pipeline and tiered them based on potential genetic liabilities to determine those best suited for clinical development. Multiple lines were then identified and iPSC and TiPSC were successfully differentiated to immune effector cells. d35 iT cells exhibited diverse phenotypes, yields, and function. These lines can then be specialized into effector cells exhibiting heightened functionality, applicable to conditions including autoimmune disorders and oncology indications, among others. Once differentiated, Century further screened the lines for their in vitro cytotoxicity and post target-engagement persistence, thereby discovering those that were most suitable for further clinical development.