Niche-specific laminins for stem cell expansion and NK cell differentiation aiming at cancer therapy

Purpose and goal

The project aimed to generate NK cells from umbilical cord blood for immunotherapy treating cancer. The parties were to find optimal conditions for reprogramming umbilical cord blood to stem cells and expand these according to the regulations that exist for clinical use of stem cells. We have fulfilled these two objectives, including creating protocols for universal stem cells that can be used by large parts of the population without immunological complications. We were to specialize these stem cells into NK cells and there we have partly succeeded but not created a validated method.

Expected results and effects

1. Determine the optimal laminin or combination needed for NK cell differentiation - results partly achieved but validation lacks. The work will continue as soon as pandemic situation allows free lab work. 2. Develop upstream and downstream production processes for CTG laminin for universal, clinical grade hiPSCs-derived NK cells - partly achieved. 3. Produce that CTG laminin large-scale - achieved. 4. Commercialize regulatory compliant CTG laminin globally - achieved. 5. Business plan for laminin-based NK cell products and applications - achieved.

Planned approach and implementation

The work were divided into 6 different work packages: WP1. Generation of safe clinical-grade master hiPS cell lines from cord blood - FINISHED WP2. Establishment of a method for the simultaneous elimination of two HLA genes in any hiPS cell line using CRISPR/Cas9 - FINISHED WP3. Differentiate hiPSCs to CD34+ hematopoietic progenitors by using laminins - ONGOING WP4. Differentiate CD34+ cells to NK cells by using laminins - FINISHED WP5. Development of cell therapy grade laminin - FINISHED WP6. Commercialisation of CTG laminin and hiPSC-NK cell protocol and product - ONGOING