iPSC-Derived CAR NK Cell Therapy Solutions

During iPSC closed system culture, challenges can include maintaining pluripotency, preventing contamination, addressing safety concerns like tumorigenicity and genetic instability, and overcoming potential scalability issues for larger-scale production.

Genome editing involves modifying, removing, or adding genetic material with the intention of altering the cells’ ability to address the intended target. Gene delivery, or transfection, refers to the process of delivering new or altered genetic material, and can be accomplished by a variety of different methods, including lipid-, viral-, and electroporation-based, each of which may be considered for a wide variety of reasons. Challenges at this step include minimizing off-target gene editing, improving transfection efficiency, and maintaining cell health and viability.

Since cell therapy applications can require a large number of cells, scale-up and closed system processing of the now-genetically-modified iPSCs is an important step. Challenges at this stage include maintaining cell viability and function, adapting to larger-scale processes, addressing potential contamination risks, and enabling aseptic conditions.

Many iPSC-based therapies are currently being investigated, with iPSC-derived NK (iNK) cells having potential utility for a variety of clinical targets. Common challenges for differentiation of iPSCs into NK cells include selecting the optimal protocol, achieving homogeneous and scalable cell populations, controlling differentiation into the desired specific cell type, and addressing regulatory, manufacturing, and logistical issues.

The end goal with this workflow is a large bank of cryopreserved cells that can be used as needed. iNK cell enrichment and banking can present challenges such as addressing regulatory concerns associated with use of feeder cells, achieving clinically relevant numbers of cells for allogeneic cell therapy applications, maintaining and expanding the population of NK cells with the correct phenotype, and minimizing cell death and impact to overall yield associated with cryopreservation (freeze/thaw).