Integrative Analysis of Proteomics and Transcriptomics Reveals the Etrb As Novel Single Target and New Combinatorial Targets for Multiple Myeloma

Background: Despite the recent introduction of next-generation immunotherapeutic agents, multiple myeloma (MM) remains an incurable disease. Increasing number targeted antigens may result in a more effective therapy by preventing antigen escape, clonal evolution and/or disease progression. Moreover, combinatorial approaches (in which activation depends on presence 2 antigens) efficient and specific treatments that limit toxicity normal tissues. In this work, we adapted algorithm integrates proteomic transcriptomic results cells to identify new possible combinations. Methods: We performed cell surface proteomics six lines based biotin labeling, protein recovery using NeutrAvidin agarose beads mass spectrometry. These were combined with gene expression studies comparing plasma B annotated tissue distribution identified proteins. The retained proteins was further studied flow cytometry malignant cells, hematopoietic stem (HSC) immune effector (T NK cells). Results: Our 209 are overexpressed from 52 could be selected for pairing. This list reduced 23 pairing rules. Flow analysis primary samples confirmed FCRL5, BCMA ICAM2 all IL6R, ETRB, SLCO5A1 PRL3 than 60%. Based single RNA-sequencing studies, ETRB is mainly expressed bone marrow its has prognostic value. By analysing HSC, T different pairs proposed can target avoid other organs. Conclusions: approach validated known integrated single-antigen or combinatorial-antigen targeting strategies novel immunotherapies.