Effect of ubenimex on the immune system of patients with hematological malignancies

The effect of in vivo administration of ubenimex (Bestatin) on the immune status of patients with hematological malignancies in remission was studied. Natural killer (NK) cell activities, lymphokine activated killer (LAK) cell activities, production of interferon-gamma (gamma-IFN) and surface antigens of peripheral lymphocytes were examined before and after administration of ubenimex. Analysis of the T, B and NK cell compartment ax conducted by assessing expression of the following antigens: CD3+CD19- (T), CD3-CD19+ (B), CD8+CD11b- (Tc), CD8+CD11b+ (Ts), CD4+Leu8-(Th), CD4+Leu8+(Ti), CD16CD57 (NK) using a 2-color flow cytometric analysis. NK and LAK activity was significantly lower in patients with hematological malignancies as compared to normal subjects. The absolute numbers of lymphocytes and NK cells were also lower than those in healthy controls. The reduced NK and LAK activity, however, was elevated after ubenimex administration. The absolute numbers of helper T cells, cytotoxic T cells and NK cells were also increased after administration of the drug. These findings were not observed in patients treated without ubenimex. Serum levels of IFN-gamma were not markedly changed after ubenimex administration. But peripheral blood mononuclear cells cultured with rIL2 showed appreciable levels of IFN-gamma production, and production increased after ubenimex administration. These results shows that ubenimex is a powerful immunomodulator that augments or restores some immune functions in patients with hematological malignancies.