Projects & Grants
| Standardization of the NK cell preparation pipeline, bioprofilling and quality control for prospective utilization of NK cells in allogeneic cell therapy | |
|---|---|
| Project Id | SGS03/LF/2024 |
| Main solver | Mgr. Klára Baďurová |
| Period | 1/2024 - 12/2024 |
| Provider | Specifický VŠ výzkum |
| State | solved |
| Anotation | Allogeneic cell therapy represents hope for oncology patients for whom other types of treatment fail. Current treatment primarily focuses on modified T lymphocytes using a chimeric antigen receptor (CAR-T). However, it can be associated with side effects (graft-versus-host disease, cytokine release syndrome, or neurotoxicity) (Celichowski et al., 2023). An alternative is NK cells (from Natural Killers), which can be developed as an "off-the-shelf" product. NK cells recognize tumor cells based on reduced expression of MHC I and respond to stress-induced proteins expressed on their surface. The utilization of NK cells or CAR-NK cells thus presents a potential alternative to CAR-T (Wolf et al., 2023). In clinical studies, donor NK cells, modified CAR-NK cells, and even the immortalized cell line NK92 are used (Meazza et al., 2023; Williams et al., 2017). The success of allogeneic NK cell therapy is determined by several factors, esp. the effector function of NK cells, their functional persistence in the body, or ongoing immunosuppressive processes (Berrien-Elliott et al., 2023). Among the drawbacks of NK cells are their shorter persistence, reduced effector function after cryopreservation, and differing anti-tumor activity of NK cells obtained from different donors (Barnes et al., 2021). These parameters can subsequently be improved through genetic modifications (CAR-NK cells) or other approaches (such as interleukin stimulation). Based on current trends, this project aims to assemble a comprehensive procedure for the preparation and basic assessment of NK cell quality from donor peripheral blood. We will monitor and evaluate differences not only among NK cells from various donors but also between donors and the NK92 cell line and, based on the knowledge gained, optimize protocols. Implementing standard methodology is also crucial for potential future genetic modifications of therapeutic NK cells and for evaluating their quality. |
