M5076 Tumor Research Articles

49] Measurement of antitumor and adjuvant effects of interferon with transplantable and other tumors in mice

This chapter deals with measurement of the effect of interferon on experimental mammary carcinoma and leukemia with emphasis on interferon's cytoreductive effect. The direct antiproliferative effect of interferon on tumor cells, and the role of interferon on activating macrophages to exert direct tumoricidal activity, natural killer cell activity are augmented in response to interferon. Interferon or interferon inducers are found to be capable of enhancing natural killer cell tumoricidal activity on YAC, M109, and MBL-2 tumor cells. Interferon, when used in conjunction with tumor cytoreductive chemotherapy is also found to exert a more beneficial effect against a murine leukemia. The enhanced therapeutic response attained by interferon adjuvant treatment may have been due to its antiproliferative effect on residual leukemia cells that escaped cytoreductive chemotherapy and/or to the interferon-enhanced macrophage and natural killer cell tumoricidal activity. Evidence indicates that interferon exerts its antiproliferative effect on tumor cells through more than one mechanism, which are (a) a direct antiproliferative effect; and (b) enhancement of the cellular immune response by direct activation of natural macrophage and natural killer cell tumoricidal activity.

Augmentation of cytotoxicity by splenic cells of pregnant or human chorionic gonadotropin-treated normal mice.

The natural killer (NK) activity, of an allogeneic tumor system, was found to be enhanced by the total splenic population of either pregnant or normal female BALB/c mice treated with human chorionic gonadotropin (HCG). The splenic population of the early pregnant (9-10 days) mice resulted in a statistically significant increase in NK activity over nonpregnant controls at all effector/target ratios tested. The mid (12-13 days) and the late (15-16 days) pregnant groups also significantly enhanced NK activity above control values at effector/target ratios of 100:1, 50:1 and 25:1. The i.v. administration of carrageenan into pregnant mice abolished the increased NK activity suggesting a putative role for the macrophage in this system. HCG administered to normal female BALB/c mice resulted in enhanced NK activity similar to that seen for the pregnant mice. This augmented NK activity does not appear to be effected by either the number or the timing of HCG administration. The augmentation of NK activity of HCG treated mice was also detected in a syngeneic system utilizing 51Cr labeled M109 tumor target cells and BALB/c effector cells.