WT1-loaded Artificial Adjuvant Vector Cell Immunotherapeutic ASP7517
wt1-loaded artificial adjuvant vector cell immunotherapeutic asp7517
A preparation of artificial adjuvant vector cells (aAVCs) composed of cells from the cell line HEK293, which is derived from human embryonic kidney cells, that are transfected with the natural killer T (NKT) immune cell receptor cluster of differentiation 1d (CD1d) and loaded with the glycolipid and CD1d ligand alpha-galactosylceramide (alpha-GalCer) on the cell surface, and loaded with the full-length tumor-associated antigen (TAA) Wilms' tumor 1 (WT1), with potential immunomodulating and antineoplastic activities. Upon administration of the WT1-loaded aAVC immunotherapeutic ASP7517, the alphaGalCer on the cell surface activates invariant NKT (iNKT) cells, thereby eliciting WT1-specific NKT cell responses against ASP7517. This in turn activates a natural killer (NK) cell response against WT1-expressing tumor cells. Also, the WT1 released from destroyed ASP7517 is taken up by antigen-presenting cells (APCs), mainly by dendritic cells (DCs), which in turn activates cytotoxic T-lymphocytes (CTL) and results in a CTL-mediated immune response against WT1-expressing tumor cells, thereby further destroying WT1-expressing tumor cells. In addition, the activation of antigen-specific memory T cells provides long-lasting anti-tumor effects against the WT1-expressing tumor cells.