GD2-specific car-T cells co-expressing the IL15 membrane form effectively lyse GD2-positive cell targets

Genetically modified T cells expressing chimeric receptors (CAR-T) have become an important tool for the treatment of the CD19+ hematological tumors. Due to a single-chain variable fragment of the antibody as a part of the CAR receptor, the cells acquire their specificity against selected tumorassociated antigens. The 3rd generation CAR also includes transmembrane, co-stimulatory domains, and tyrosine activation motifs derived from CD3z. This design allows the T-cells to recognize antigens in an MHC-independent manner and provides activation and release of cytotoxic cytokines upon recognition of the target. There are several limitations to the effective use of the CAR-T cells for the treatment of solid tumors, among them tumor stroma suppressive activity, poor persistence, and migration of effectors in a tissue. The aim of our project is to improve the CAR-T cells targeting at GD2 and L1CAM neuroblastoma antigens by co-expression with membrane-anchored cytokines.