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Background Monoclonal antibodies (mAbs) induce therapeutic effect via antibody-dependent cell-mediated cytotoxicity (ADCC) and have long been standard of care in oncology. Recently, tyrosine kinase inhibitor (TKI) drugs have improved clinical outcomes for patients. In many indications, mAb/TKI combination is recommended, and suggests that such combinations enhance therapeutic effect. Welt Bio-Molecular Pharmaceutical (WBMP) generates mAbs that block transmembrane signal transmission by binding to key driver receptors. Such drugs may allow for kinase inhibition and ADCC to be achieved by one modality. Our lead mAb, WBMP-4, binds to membrane-bound IgM, within the B-cell Receptor (BCR), and induces cell growth inhibition (low doses) and apoptosis (high doses) in IgM-expressing B-cell malignancies. Here we present the results of kinome and protein expression studies that characterize the mechanism of action of WBMP-4.Methods We evaluated kinase activity in lymphoma cells treated with WBMP-4 (at 5 and 20 ug/mL, and 6 and 24 hours) via the PamGene kinase assay. This assay measures kinase activity in cell lysates using a microarray chip containing peptide sequences that serve as substrate for 189 phosphotyrosine sites on well-characterized proteins. Additionally, we measured protein expression and phosphorylation of key targets downstream of the BCR via western blot analyses.Results Our kinome analysis reveals widespread kinase modulation following WBMP-4 treatment, with >180 of 189 phosphosites showing a significant change in phosphorylation signal intensity (>153 decreased). Western blot analyses similarly show changes in phosphorylation of kinases (ZAP70, mTOR, AKT, and MEK). However, we also find decreased protein expression of CD79b, ZAP70, BTK, MEK, Myc, and increased LCK following WBMP-4 treatment.Conclusions WBMP-4 impacts kinase activity across signaling pathways upon binding to the BCR’s mIgM, the vast majority of which are downregulated. Additionally, protein expression is impacted in several kinases directly downstream of the BCR. We hypothesize that kinase inhibition induced by WBMP-4 modulates transcription factor activity, and resultantly, protein expression, which maintains growth inhibition signaling and prevents recovery signals, determining the fate of the cells. Further analyses of WBMP-4 will test the effects of this mAb in an in vivo model, to determine whether the addition of immune-mediated effects (via ADCC) can improve therapeutic outcomes. WBMP-4’s global kinase inhibition encompasses the effects of approved inhibitor drugs (i.e. BTK, PI3K, and Bcl-2 inhibitors), and should be more tumor-restrictive; WBMP-4 only affects IgM-expressing B-cells, sparing healthy B-cells that express other classes of Ig. This tumor specificity and potent inhibitory effects make WBMP-4 a promising clinical candidate.