Projects & Grants
| Targeting Multiple Myeloma with NK Cells Derived from hiPSCs | |
|---|---|
| Project Id | SGS05/LF/2026 |
| Main solver | Mgr. Tereza Fantová |
| Period | 1/2026 - 12/2026 |
| Provider | Specifický VŠ výzkum |
| State | solved |
| Anotation | Multiple myeloma (MM) is a hematological malignancy of plasma cells arising in the bone marrow and represents the second most common type of hematologic cancer. Although patient survival has improved over recent decades, disease relapse remains almost inevitable, and many patients progress to an aggressive, treatment-resistant form. The development of cell-based therapies, particularly employing T lymphocytes and natural killer (NK) cells, has introduced new therapeutic opportunities; however, these approaches still face challenges related to donor variability, limited cell availability, and insufficient cellular persistence. To overcome these limitations, we propose the use of commercially available human induced pluripotent stem cells (hiPSCs) as an easily accessible, unlimited, and standardized source of induced NK (iNK) cells for MM therapy. This strategy would eliminate donor-dependent variability and enable large-scale production of therapeutic cells. This research will focus on three main areas: (1) Optimization of a two-stage differentiation process to generate functional iNK cells from commercially available hiPSCs. iNK cells will be phenotypically characterized by flow cytometry and functionally tested against MM cell lines. (2) Genetic engineering to create hypoimmunogenic iNK cells with enhanced antitumor activity. The cells will be modified to overexpress PD-L1 and to undergo PD-1 knockout to increase immune tolerance. They will further be engineered to express a BMCA-specific chimeric antigen receptor (CAR) and TRAIL, strengthening their ability to selectively induce apoptosis in MM cells. (3) Evaluation of the translational potential of iNK cells will be performed through co-culture with peripheral blood mononuclear cells and primary MM cells derived from patients. This project targets a rapidly developing area of cellular immunotherapy and represents a potential step toward the development of a universal, safe, and effective treatment for MM. |
| Total Costs | 254 100 CZK |
