Non metastasis protein 2 (NME2) is a potential target for leukemia-specific immunotherapy

Abstract:Background: NME2 is an immunogenic overexpressed tumor-associated antigen in chronic myeloid leukemia (CML). We evaluated NME2’s antigenicity in common HLA-backgrounds as a potential target for CML-specific immunotherapy. Methods: NME2-specific cytotoxic T-lymphocytes (CTL) were generated by stimulating cultured PBMCs with artificial antigen presenting cells (aAPC) expressing NME2 and the appropriate HLA-A antigen. Cultured PBMCs were obtained from healthy donors or CML-patients and priming with aAPCs was repeated weekly. IFNγ production from CD8+CTLs was evaluated by ELISpot assays. Results: NME2-specific CTLs were successfully generated both from healthy donors and from CML patients after hematopoietic stem cell transplantation. NME2-specific recognition by CTLs was HLA class I restricted (HLA-A 02, 03, 24) with no significant differences between the HLA-A backgrounds tested. The T315I TKI resistance mutation BCR::ABL1 did not affect susceptibility to CTL-mediated killing.Conclusions: NME2-specific CTLs can eradicate CML progenitor cells remaining after TKI-therapy or HSCT. Immunotherapy targeting NME2 may complement existing therapies.