Researchers have engineered CAR-NK (Chimeric Antigen Receptor-Natural Killer) cells to target CD5-positive hematological malignancies. These engineered cells incorporate two VH domains, a CD8 hinge, a transmembrane domain, a 4-1BB co-stimulatory domain, and a CD3ζ activation domain. Secretory IL15 was included to enhance CAR-NK cell proliferation, alongside an HSV-TK gene as a safety switch.
The engineered CAR-NK cells have demonstrated cytotoxicity against primary tumor cells and CD5+ leukemia cells in vitro. In vivo studies using NCG mice injected with Jurkat-Luci cells indicated that CAR-NK cell treatment reduced leukemic burden and prolonged survival compared to control groups. The expression of CD5, HLA-I, HLA-II, MICA/MICB, and ULBPS on tumor cell lines and primary tumor cells was analyzed by flow cytometry.
Cytolysis of primary tumor cells and T cells from healthy donors was determined by flow cytometry. CAR-NK cells expressing HSV-TK were treated with GCV, and cell counts were analyzed to assess the proportion of CAR-positive cells. These early findings highlight the potential of CAR-NK cell therapy as a future treatment strategy for CD5+ hematological malignancies. Further research is needed to confirm these results and evaluate the safety and efficacy in human clinical trials.