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

2016

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 .

NTNU