Abstract Natural Killer/ T cell Lymphoma (NKTL), a subtype of non-Hodgkin lymphoma, is an Epstein–Barr virus (EBV) associated lympho-proliferative disease more prevalent in Asia and South America. It develops from transformation of natural killer (NK) -cells or cytotoxic T-cells. Current treatments options are inadequate with treatments such as conventional radiotherapy or chemotherapy having limited efficacy. Efficacy of newer promising therapies such as targeted therapies or immunotherapies has been less than ideal in clinical trials likely due to heterogeneous nature of disease. Novel treatments which are more efficacious will have to be formulated. Immunotherapy has been growing in popularity which can be attributed to higher specificity and less cytotoxicity. Hence, this project aims to develop a novel antibody-based therapy against NKTL to improve outcomes of NKTLs patients. First step in antibody-based therapy development involves identification of suitable targets. Plasma membrane proteins are a special class of biomolecules present on cellular membrane which are appealing therapeutic targets due to their accessibility and importance in cellular functions. Here, we utilized bottom-up label-free mass spectrometry plasma membrane profiling with the use of aminooxy-biotin and streptavidin beads for the enrichment of surface proteins to characterize the plasma membrane landscape of NKTL. NKTL cell lines with different characteristics were utilized in the analysis to better capture variations in the surfaceome. To further increase the stringency of the analysis, a unique method of membrane protein annotation was devised by looking at different public databases. Targets with highest immunotherapeutic potentials were revealed through ranking based on their specificity and accessibility. Further works including internalization assays and antibody dependent effector functions were studied for the top target which continued showing high therapeutic potential. As such, our work characterized the plasma membrane landscape of NKTL and shed light on immunotherapeutic targets with potential to become novel treatments for this dreadful disease. Citation Format: Ern Sen Chew, Nurulhuda Binte Mustafa 2024 Nov 13-15; Singapore. Philadelphia (PA): AACR; Cancer Res 2025;85 (15Suppl): Abstract nr P07.
Chew et al. (Fri,) studied this question.