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

Cell Death & Disease
Pascal LeclairChinten James Lim

Abstract

CD47 is a cell-surface marker well recognized for its anti-phagocytic functions. As such, an emerging avenue for targeted cancer therapies involves neutralizing the anti-phagocytic function using monoclonal antibodies (mAbs) to enhance tumour cell immunogenicity. A lesser known consequence of CD47 receptor ligation is the direct induction of tumour cell death. While several mAbs and their derivatives with this property have been studied, the best characterized is the commercially available mAb B6H12, which requires immobilization for induction of cell death. Here, we describe a commercially available mAb, CC2C6, which induces T-cell acute lymphoblastic leukemia (ALL) cell death in soluble form. Soluble CC2C6 induces CD47-dependent cell death in a manner consistent with immobilized B6H12, which is characterized by mitochondrial deficiencies but is independent of caspase activation. Titration studies indicated that CC2C6 shares a common CD47-epitope with B6H12. Importantly, CC2C6 retains the anti-phagocytic neutralizing function, thus possessing dual anti-tumour properties. Although CD47-ligation induced cell death occurs in a caspase-independent manner, CC2C6 was found to stimulate increases in Mcl-1 and NOXA levels, two Bcl-2 f...Continue Reading

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Citations

Sep 25, 2019·Nature Biomedical Engineering·Barbara MairShana O Kelley
Feb 12, 2020·Cancer Science·Pascal LeclairChinten James Lim
Sep 25, 2019·Innate Immunity·Sharareh GholaminSamuel H Cheshier
Jul 6, 2019·Journal of Oncology·Ana Carolina Martínez-TorresCristina Rodríguez-Padilla
Feb 23, 2020·Frontiers in Immunology·Wenting ZhangHua Jin
Nov 22, 2018·Cancer Science·Ashanti Concepción Uscanga-PalomequeCristina Rodríguez-Padilla
Sep 5, 2020·Antibodies·Lamin B ChamKarl S Lang
Jun 14, 2019·Frontiers in Oncology·Chi-Chao LiuChinten James Lim
Aug 31, 2019·Hematology/oncology Clinics of North America·Zhen Mei, Geoffrey D Wool
Nov 24, 2020·Animal Cells and Systems·Pascal Leclair, Chinten James Lim
Jul 2, 2020·Trends in Immunology·Ramon Arens, Ferenc A Scheeren

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Methods Mentioned

BETA
transfections
flow cytometry
xenograft

Clinical Trials Mentioned

NCT02216409
NCT02678338
NCT02953509
NCT03248479
NCT02953782

Software Mentioned

Metamorph®
FlowJo Tree Star

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