Applied StemCell, a CRO/CDMO specializing in genome editing technology and iPSC expertise, has launched two new hypoimmunogenic human induced pluripotent stem cell (hiPSC) products aimed at accelerating the development of next-generation allogeneic cell therapies. The announcement, made on May 20, 2025, introduces tools designed to address one of the most significant challenges in cell therapy development: immune rejection.
The new research-use-only (RUO) products—ActiCells™ RUO Hypo hiPSCs (Cat.# ASE-9550) and ActiCells™ RUO TARGATT™ Hypo hiPSC Knock-in Kit (Cat.# AST-9650)—combine reduced immunogenicity with robust pluripotency and genome engineering capabilities to facilitate the development of "off-the-shelf" cell therapies.
Innovative Genetic Modifications to Evade Immune Rejection
Both products feature strategic genetic modifications that address a fundamental challenge in allogeneic cell therapy: immune system recognition and rejection of transplanted cells. The hiPSCs are engineered with a double knockout of B2M and CIITA genes, effectively eliminating cell surface expression of both HLA class I and class II molecules.
"Our latest ActiCells products demonstrate how Applied StemCell's deep expertise in iPSC biology and genome editing enables us to create tools that push the boundaries of what's possible in allogeneic therapy," said Ruby Tsai, Ph.D., CEO of Applied StemCell. "With these new hypoimmunogenic iPSC platforms, researchers have the flexibility to rapidly build, test, and optimize cell therapies that are designed to evade immune rejection."
The cells are reprogrammed from CD34+ umbilical cord blood cells, specifically selected for their low mutational burden and reduced immune activation properties. This source material provides an additional advantage for therapeutic development by minimizing the risk of unwanted mutations that could affect safety or efficacy.
Complementary Products for Different Research Needs
The two products offer researchers different entry points into hypoimmunogenic cell therapy development. The ActiCells™ RUO Hypo hiPSCs provide a ready-to-use, transgene-free cell line that is fully characterized, pluripotent, and prepared for additional genome engineering as needed.
For researchers requiring immediate knock-in capabilities, the ActiCells™ RUO TARGATT™ Hypo hiPSC Knock-in Kit includes the same hypoimmunogenic cell line pre-engineered with TARGATT™ large knock-in technology at the H11 safe harbor locus. This kit also contains cloning and integrase plasmids that enable site-specific insertion of genetic payloads up to 20 kb with reliable expression and minimal risk of gene silencing or off-target effects.
"These two complementary products allow researchers to choose the format that best fits their project timelines and resources," explained Dr. Tsai. "Whether you're building custom engineered lines in your own lab or partnering with us for iPSC gene editing services, you can count on ActiCells to deliver consistent quality and advanced functionality."
Bridging Research and Clinical Development
A key advantage of these new products is their isogenic match to forthcoming GMP-grade versions, offering researchers a seamless path from early research to clinical development. This alignment helps eliminate potential variables when transitioning from research to clinical manufacturing, potentially saving time and resources in the development pipeline.
The launch of these hypoimmunogenic hiPSC products represents a significant advancement in the tools available for allogeneic cell therapy development. By addressing the immune rejection challenge that has historically limited the broad application of allogeneic approaches, these products may help accelerate the development of next-generation cell therapies for a range of conditions.
Implications for Allogeneic Cell Therapy Field
The introduction of these hypoimmunogenic hiPSC products comes at a critical time for the cell therapy field. While autologous cell therapies (using a patient's own cells) have shown remarkable clinical success, they face significant manufacturing challenges, high costs, and production delays. Allogeneic approaches—using cells from donors to create standardized, off-the-shelf products—offer potential solutions to these limitations but have been hampered by immune rejection concerns.
By providing tools that specifically address immune evasion while maintaining pluripotency and genetic engineering capabilities, Applied StemCell's new products may help researchers overcome a key technical hurdle in developing commercially viable allogeneic cell therapies.
The B2M/CIITA double knockout strategy employed in these products represents a sophisticated approach to immune evasion. By eliminating HLA class I molecules (through B2M knockout) and preventing HLA class II expression (through CIITA knockout), these cells are designed to avoid recognition by both CD8+ and CD4+ T cells, key mediators of cellular immune rejection.
