Next Generation Sequencing Facilitates Quantitative Analysis of Transcriptomes of MM cells after M2 Treatment

Targeted immunotherapies based on monoclonal antibodies have continued to show clinical activities in patients with multiple myeloma (MM). A novel antibody drug conjugate targeting BCMA armed with a DNA cross-linking pyrrolobenzodiazepine PBD dimer tesirine M2, is currently under clinical development for MM. M2 has demonstrated potent cytotoxicity against MM cells in bulk as well as quiescent tumor-initiating cells in in vitro and in vivo preclinical studies. We here further investigate its effects on transcriptional changes in MM cells prior to apoptosis and identify molecular events regulating its potential immunomodulation to further upregulate its efficacy. RNA sequencing followed by gene set enrichment analysis in MM cells treated with M2 vs control vehicle at sub-lethal concentrations reveal that M2 can induce interferon-regulated genes dependent on DNA damage-initiated signaling pathways, providing new molecular insight into its mechanisms of action in MM in the bone marrow microenvironment. Overall design: H929 cells were treated with M2 vs control vehicle (solvent). Two biological replicates per conition were obtained.