Browsing by Subject "Immunotheraphy"

Cell-based immunotherapies offer highly targeted treatment, potentially leading to higher response rates and reduced long-term side effects compared to chemotherapy. In the clinics, chimeric antigen receptor T-cell therapies are already being used as neo-adjuvant therapy for certain types of cancer, however, they can have significant drawbacks. Natural killer (NK) cells have emerged as a promising alternative option for targeting various hematological and solid tumors. Unlike T-cells, NK-cells do not need prior sensitization to the target and have the potential to be used as a allogeneic, ‘Off-the-shelf’, product. Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. Chemotherapy and small molecule drugs are typically used for the treatment of AML. However, the prognosis for relapsed or refractory AML patients remains unsatisfactory. Therefore, a collaborative project between the Helsinki Central Hospital and the Advanced Cell Therapy Center from the Finnish Red Cross, Blood Service was initiated to develop clinical-NK products targeting high-risk AML patients in Finland. A reliable and suitable in vitro cytotoxicity assay was required to assess the efficacy of NK cells before they could be given to AML patients. A luminescence-based method utilizing cellular ATP, was found to be the best performing method considering constraints such as the limited amount of patient material. AML blasts were successfully isolated from the whole blood of patients using CD33 microbeads and maintained in a composition of cytokines mix in RPMI media. The cytotoxicity assay paired with statistical analysis was able to identify significant differences in cytotoxic efficacy between NK cells from different donors. Additionally, results indicate improved cytotoxic efficacy in activated NK cells compared to non-activated NK cells, highlighting the usefulness of activated NK cells for use in the clinics.