Pappalysin-1 T cell receptor transgenic allo-restricted T cells kill Ewing sarcoma in vitro and in vivo.

ABSTRACT: Pregnancy-associated plasma protein-A (PAPPA), also known as pappalysin, is a member of the insulin-like growth factor (IGF) family. PAPPA acts as a protease, cleaving IGF inhibitors, i.e., IGF binding proteins (IGFBPs), thereby setting free IGFs. The insulin/IGF-axis is involved in cancer in general and in Ewing sarcoma (ES) in particular. ES is a highly malignant bone tumor characterized by early metastatic spread. PAPPA is associated with various cancers. It is overexpressed and required for proliferation in ES. PAPPA also stimulates normal bone growth. We isolated HLA-A*02:01⁺/peptide-restricted T cells from A*02:01^- healthy donors directed against PAPPA, generated by priming with A*02:01⁺ PAPPA peptide loaded dendritic cells. After TCR identification,

SUBMITTER: Kirschner A 

PROVIDER: S-EPMC5353903 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature