CD47-ligation induced cell death in T-acute lymphoblastic leukemia

• DOI: 10.1038/s41419-018-0601-2
• Publication Date: 2018-05-10T11:41:40Z
• Authors: Pascal Leclair; Chi-Chao Liu; Mahdis Monajemi; Gregor S. Reid; Laura M. Sly; Chinten James Lim
• Keywords: CD47

Abstract CD47 is a cell-surface marker well recognized for its anti-phagocytic functions. As such, an emerging avenue targeted cancer therapies involves neutralizing the function using monoclonal antibodies (mAbs) to enhance tumour cell immunogenicity. A lesser known consequence of receptor ligation direct induction death. While several mAbs and their derivatives with this property have been studied, best characterized commercially available mAb B6H12, which requires immobilization Here, we describe mAb, CC2C6, induces T-cell acute lymphoblastic leukemia (ALL) death in soluble form. Soluble CC2C6 CD47-dependent manner consistent immobilized by mitochondrial deficiencies but independent caspase activation. Titration studies indicated that shares common CD47-epitope B6H12. Importantly, retains function, thus possessing dual anti-tumour properties. Although CD47-ligation induced occurs caspase-independent manner, was found stimulate increases Mcl-1 NOXA levels, two Bcl-2 family proteins govern intrinsic apoptosis pathway. Further analysis revealed ratio Mcl-1:NOXA were minimally altered cells treated comparison agents caspase-dependent alter favour NOXA. Finally, can synergize low dose chemotherapeutic induce classical apoptosis, giving rise possibility effective combination treatment reduced long-term sequelae associated high-dose chemotherapies childhood ALL.