Emerging role of protectin (CD59) in humoral immunotherapy of solid malignancies.

: Over the past two decades, complement (C)-activating monoclonal antibodies (mAb), directed to specific tumor-associated antigens (TAA), have been extensively utilized for passive immunotherapy of solid tumors of different histology. However, the clinical outcome of this therapeutic approach has been substantially disappointing; antigenic heterogeneity of neoplastic cells and their limited accessibility by therapeutic mAb, have been provided as substantial explanations for the poor clinical results obtained. Nevertheless, in light of the recent advances in the knowledge of the mechanisms regulating C-activity, it begins to be evident that membrane and soluble C-inhibitory proteins play a key role in the protection of neoplastic cells from C-attack, providing additional insights on biological features of transformed cells that may hamper the clinical efficacy of humoral immunotherapy. Among C-regulatory proteins investigated, this review will focus on protectin (CD59) that represents the main restriction factor of C-susceptibility of neoplastic cells from solid malignancies. In view of the functional role of CD59, we will describe its tissue distribution and biological features in malignant neoplasms; major emphasis will be given to cutaneous melanoma, in which the C-regulatory role of CD59 has been extensively investigated, and clinical approaches of humoral immunotherapy have been implemented. According to the available data, the foreseeable strategies to improve the therapeutic efficacy of humoral immunotherapy of solid malignancies will be discussed.