EFFICACY OF TNF-ALPHA GENE-TRANSDUCED TUMOR-CELLS IN TREATMENT OF ESTABLISHED IN-VIVO TUMOR

The therapeutic effect of TNF gene-transduced mouse fibrosarcoma cells (Meth-A: C5) on pre-inoculated parental cells (Meth-A: MO) was studie d. Subcutaneous (s.c.) transplantation of MO cells into one flank of s yngeneic BALB/c mice was followed by s.c. injection of irradiated MO o r C5 into the opposite flank I week later. The initial MO tumor (T-MO) completely regressed in C5-vaccinated mice, whereas in MO-vaccinated mice continuous growth of T-MO was observed. When a similar experiment was carried out in SCID mice, no regression of T-MO was observed, sug gesting that the tumor regression in BALB/c mice was not due to direct anti-tumor activity of TNF secreted from C5, but to systemic immunity . Regression of the rechallenged MO tumor was observed in mice which h ad shown T-MO regression by C5 vaccination, but rechallenged Colon 26 cells (syngeneic to BALB/c mice) continued to grow, indicating a speci fic immunity to Meth-A cells. The systemic immunity evoked in C5-vacci nated mice was directly demonstrated by enhanced killer activities of LAK and CTL with a proliferation of T-cell population in their splenoc ytes. Abrogation of the therapeutic effect of C5 vaccination with anti -Thy 1 and anti-Lyt 2 also demonstrates the involvement of cellular im munity in tumor regression. (C) 1995 Wiley-Liss, Inc.