The effectiveness of active specific immunotherapy using interferon-gamma-gene-transduced tumor cells in a murine tumor model.

Abstract

Active specific immunotherapy was examined in BALB/c mice using sonicated tumor extract(SE) from plasmacytoma MOPC104E or interferon-gamma-(IFN-gamma)-gene-transduced MOPC104E (Mu gamma), employing interleukin-1 (IL-1) as an adjuvant. Subcutaneous (s.c.) MOPC104E tumor growth was significantly suppressed in mice given a single preimmunization of IL-1 plus Mu gamma-SE, 9 days prior to inoculation, whereas the tumor growth in mice similarly pretreated with IL-1 alone or IL-1 plus MOPC104E-SE(MOPC-SE) was not affected; the mean tumor diameters on day 21 being 6.8 mm, 15.3 mm, and 13.2 mm, respectively. Two-dose preimmunization with Mu gamma-SE alone or IL-1 alone given 10 and 7 days prior to s.c. inoculation also resulted in profound suppression of tumor growth compared to the control. As postsurgical immunization, MOPC104E cells were injected into the foot pads of mice, followed by amputation of the tumor-bearing foot 20 days later, then treatment with IL-1 plus MOPC-SE or IL-1 plus Mu gamma-SE on days 4, 7, and 10 after the amputation. The mean survival of the mice treated with IL-1 plus Mu gamma-SE was significantly prolonged compared to that of the mice treated with IL-1 plus MOPC-SE, at 90.3 days vs 40.9 days, respectively (P < 0.05 by the Cox-Mantel test). These results suggest that SE prepared from IFN-gamma-gene-transduced MOPC104E is more effective for active specific immunotherapy than SE prepared from MOPC104E.