Expression of two Cell Membrane Proteins, CD37 and PD-L1, in Acute Myeloid Leukemia Cell Lines

Abstract

The standard chemotherapy treatment given to newly diagnosed Acute Myeloid Leukemia ( AML ) patients have remained practi- cally the same for the last forty years, and is poorly tolerated by the older patients. Several new therapies are under development, among other targeting therapies using antibodies, and thera- pies directed towards immune checkpoints. Antibodies target- ing CD33 seem promising, and recently a therapeutic antibody targeting CD37 has entered clinical trial phase I. In this mas- ter thesis, the binding of another anti CD37 antibody, NNV003, was measured in seven AML cell lines to find out if NNV003 could be a potential new therapy for AML . To investigate if in- hibiting immune checkpoints could be used in AML treatments, the expression of the immune checkpoint molecule Programmed Death-Ligand 1 ( PD-L1 ) was evaluated in these cell lines. Flow cy- tometry and fluorescently labeled antibodies were used to mea- sure the CD37 and the PD-L1 expression. In addition, the pos- sibility of a combination treatment including both the NNV003 antibody and an anti PD-L1 antibody was assessed, by investi- gating if the PD-L1 expression was upregulated after incubation with NNV003. NNV003 bound to all the AML cell lines, although at a lower level than in lymphoma cell lines. The apoptosis in- duced by NNV003 incubation was low or non existing in AML cell lines. Only two AML cell lines seemed to have a PD-L1 expres- sion, though very low. There was no strong correlation between the NNV003 binding to CD37 and the expression of PD-L1 , but a possible combination therapy can not be ruled out as the in vitro experiments done in this study do not reflect the actual cir- cumstances of cancer cells in a tumour microenvironment. This first in vitro study of NNV003 binding to CD37 in AML cell lines show promising results for using an Antibody Radionu- clide Conjugate ( ARC ) or Antibody Drug Conjugate ( ADC ) based on NNV003 as a new targeting therapy against AML .