Anti-tumoral effect of GM-CSF with or without cytokines and monoclonal antibodies in solid tumors.

Cytotoxicity is an important function of the immune system that results in destruction of cellular targets by humoral and cellular mechanisms. The functional capacity of granulocytes, lymphocytes and macrophages are of significance for cancer patients because of the ability of these cells to exhibit anti-tumor activity. The hallmark of immune cytotoxicity is the recognition and destruction of selected targets by humoral and cellular effects that distinguish between targets and normal cells. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine with potential to be an anti-neoplastic cytokine. GM-CSF induces: (1) differentiation of monocytes to large macrophage like cells; (2) augmentation of MHC class II antigen expression on monocytes; (3) enhancement in vitro of macrophage and granulocyte natural cytotoxicity and ADCC; and (4) increased expression of adhesion molecules and granulocytes and monocytes. GM-CSF also cooperates with other cytokines in the expansion of specific T cells. Several experimental and clinical studies have demonstrated the anti-neoplastic effects of GM-CSF alone or in combination with cytokines or/and monoclonal antibody. Interestingly, the future might see the combination of GM-CSF and mouse monoclonal antibody MAb17-1A in the adjuvant setting in colon- and/or rectal carcinoma patients.