Regression of intracerebral rat glioma isografts by therapeutic subcutaneous immunization with interferon-gamma, interleukin-7, or B7-1-transfected tumor cells

Progress in the definition of the roles of various costimulators and cytoki nes in determining the type and height of immune responses has made it impo rtant to explore genetically altered tumor cells expressing such molecules for therapeutic immunizations. We have studied the effect of therapeutic su bcutaneous (s.c.) immunizations on the growth of preexisting intracerebral brain tumor isografts in the rat. Transfectant glioma cell clones expressin g either rat interferon-gamma (IFN-gamma), rat interleukin-7 (IL-7), or rat B7-1 were selected. After irradiation (80 Cy) the clones were used for imm unization (administered in up to four s.c. doses in a hind leg over 14-day intervals starting 1 day after the intracranial isografting of the parental tumor). Significant growth inhibition of the intracerebral parental tumors was induced by transfectants expressing IFN-gamma and IL-7, respectively. The strongest effect was observed with IFN-gamma-expressing cells, resultin g in cures in 37% of the males and in 100% of the females. Immunization wit h IL-7 had a similar, strong initial effect, with significantly prolonged s urvival in the majority of the rats but a lower final cure rate (survival f or >150 days). The B7-1-expressing tumor clones induced cures in seven of e ight female rats; however, no cures were seen in the male rats. It was also shown that the B7-1-expressing cells were themselves strongly immunogenic in female rats, requiring high cell numbers to result in a progressively gr owing tumor upon s.c. isografting; this was not the case in male rats. As a whole, the results imply that despite the unfavorable location of intracer ebral tumors, therapeutic s.c. immunizations with certain types of genetica lly altered tumor cells can induce complete regressions with permanent surv ival and without gross neurological or other apparent signs of brain damage . The present results demonstrate complete regressions when immunizations a re initiated shortly after intracranial isografting, when the intracerebral tumor is small.