Treatment of 9L gliosarcoma with IL-4 producing 9L vaccine

We have demonstrated previously that interleukin-4 (IL-4) promotes T-cell dependent anti-tumor activity against the 9L giiosarcoma in Fischer rats. 9L gliosarcoma cells transfected with an mIL-4 cDNA and secreting 20 ng IL-4/48h/106 cells are 97% growth inhibited afler implantation in the Fischer rat central nervous system and are eliminated, following a brief period of growth, within 30 days after subcutaneous (sc) implantation in Fischer rats. Further, Fischer rats vaccinated with 2 x l O6 9L-IL4 cells are immune to subsequent subcutaneous or jntracerebral challenge with parental 9L tumor at 30 days. Based on these results, we tested the efficacy of 9L-IL4 transduced cells as a treatment for established intracerebral 9L tumor. Twenty-four Fischer rats received 5 × 10⁴ 9L cells intracerebrally via stereotactic microinjection. Three days later, rats in the treatment group (n=18) were vaccinated subcutaneously with 2 x 106 9L-1L4 cells and rats in the control group (n=6) received a subcutaneous injection of HBSS. Median survival was 31 days in the control group and 56 days in the treatment group (p=.0089). Of greater significance, 9/18 rats in the treatment group are alive at greater than 120 days and show no evidence of neurologic dysfunction or systemic illness, while, as expected, mortality was 100% in the control group. Histologie studies have shown that whereas only a sparse number of 9L tumor infiltrating mononuclear cells are visible in control rats at day 17, intracranial 9L tumors in treated rats are densely infiltrated by mononuclear cells. These data suggest that the systemic immune response generated in Fischer rats by subcutaneous vaccination with 9L-IL4 cells can lead to the infiltration of intracranial tumor by effector cells capable of some level of activity against 9L. They also show that 9L cells modified by cytokine gene transduction to express IL-4 can,be used to treat established, intracrpnial 9L tumors.