Expression of two Cell Membrane Proteins, CD37 and PD-L1, in Acute Myeloid Leukemia Cell Lines
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- Institutt for fysikk 
The standard chemotherapy treatment given to newly diagnosedAcute Myeloid Leukemia ( AML ) patients have remained practi-cally the same for the last forty years, and is poorly tolerated bythe 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 antibodytargeting 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 NNV003could 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 ProgrammedDeath-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 NNV003antibody and an anti PD-L1 antibody was assessed, by investi-gating if the PD-L1 expression was upregulated after incubationwith NNV003. NNV003 bound to all the AML cell lines, althoughat a lower level than in lymphoma cell lines. The apoptosis in-duced by NNV003 incubation was low or non existing in AMLcell lines. Only two AML cell lines seemed to have a PD-L1 expres-sion, though very low. There was no strong correlation betweenthe NNV003 binding to CD37 and the expression of PD-L1 , buta possible combination therapy can not be ruled out as the invitro experiments done in this study do not reflect the actual cir-cumstances of cancer cells in a tumour microenvironment. Thisfirst in vitro study of NNV003 binding to CD37 in AML celllines show promising results for using an Antibody Radionu-clide Conjugate ( ARC ) or Antibody Drug Conjugate ( ADC ) basedon NNV003 as a new targeting therapy against AML .