Humoral immunotherapy of multiple myeloma: perspectives and perplexities

mportance of the field: Multiple myeloma (MM) is a hematological malignancy still remaining incurable despite the various therapies available, mainly because of the high fraction of refractory/relapsing cases. Therefore, the development of novel therapeutic approaches is urgently needed to overcome conventional treatment resistance. Areas covered in this review: In the era of targeted therapies, treatments combining a high specificity for neoplastic cells and the capability to interfere with environmental signals should be regarded as the weapons of choice. Monoclonal antibody (mAb)-based humoral immunotherapy could satisfy both these requirements when applied to MM. Indeed, many of the molecules expressed on MM cells, such as CD38, CD40, CD49d, CD138 and CD162 are involved in the adhesive dynamics regulating the crosstalk between MM and the BM-microenvironment. What the reader will gain: In this study we review those MM-associated molecules that have shown promising antitumor effects as targets of speci- fic mAbs in preclinical settings, thus deserving to be considered for clinical investigation. Take home message: mAbs directed against MM-associated adhesion markers should be taken into account in clinical practice, since they could possibly rep- resent the best available combination of tumor cytotoxicity, environmental signal deprivation and immune system redirection.