An immunoglobulin (Ig) G1 humanized monoclonal antibody targeting human R-spondin 3 (RSPO3), with potential immunostimulating and antineoplastic activities. Upon intravenous administration, the anti-RSPO3 monoclonal antibody OMP-131R10 targets and binds to RSPO3 expressed on tumor cells. This prevents the activation of RSPO3, and inhibits both the binding of RSPO3 to leucine-rich repeat-containing G-coupled receptors (LGRs) and the activation of the RSPO-LGR pathway. This may result in an inhibition of both cancer stem cell (CSC) survival and the proliferation of cancer cells in which this pathway is overactivated. The RSPO-LGR pathway is a CSC pathway activated in a variety of cancer cell types.