Gamma-globulin inhibits tumor spread in mice

Intravenous (i.v.) Ig is the human serum Ig fraction that is mainly composed of IgG prepared from plasma pools of over 15,000 healthy blood donors and is suitable for i.v. use. High-dose i.v. Ig is currently used to treat patients with diverse autoimmune conditions. Autoimmunity and malignancy co-exist frequently, and share etiological and pathological mechanisms. Since the two diseases are similarly treated, we studied the efficacy of i.v. Ig as a treatment for malignant conditions. The administration of i.v. Ig to mice inoculated i.v. with melanoma or sarcoma cells induced a statistically significant inhibition of metastatic lung foci and prolongation of survival time. Similar results were seen with SCID mice inoculated with SK-28 human melanoma cells. In a different model, melanoma was induced in the foot pad, followed by leg amputation, after the development of the tumor lesion. A lower number of melanoma recurrences and prolongation of survival time were demonstrated in the i.v., Ig-treated groups. In vitro studies revealed that i.v. Ig was found to stimulate the production of IL-12, an anti-tumor and anti-angiogenic cytokine. Moreover, it enhanced NK cell activity, thus explaining its beneficial effect in SCID mice (which lack B and T but possess NK cells). The results indicate that i.v., Ig acts as an anti-tumor agent. Since it has only minor side effects and is used extensively for other clinical conditions, i.v., Ig may be considered as a potential therapy for the prevention of tumor spread in humans.