Humoral immunotherapy of multiple myeloma: perspectives and perplexities

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.

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.

In this study we review those MM-associated molecules that have shown promising antitumor effects as targets of specific mAbs in preclinical settings, thus deserving to be considered for clinical investigation.

mAbs directed against MM-associated adhesion markers should be taken into account in clinical practice, since they could possibly represent the best available combination of tumor cytotoxicity, environmental signal deprivation and immune system redirection.