INTERLEUKIN-2 GENE-MODIFIED ALLOGENEIC-TUMOR CELLS FOR TREATMENT OF RELAPSED NEUROBLASTOMA

Tumor cells that have been genetically modified to express immunostimu latory genes will induce effective antitumor responses in a range of s yngeneic animal models. For human applications, transduced autologous tumor cell lines are often difficult or impossible to prepare, so that there are strong incentives for substituting a standardized allogenei c tumor cell line. However, such lines may be inferior immunogens if t hey differ from host tumors in the antigens they express. We have eval uated the safety, immunostimulatory, and antitumor activity of an inte rleukin-2-secreting allogeneic neuroblastoma cell line in 12 children with relapsed stage IV neuroblastoma, They received two to four subcut aneous injections of cells in a dose-escalating schedule, up to a maxi mum of 10(8) cells per injection. There was induration and pruritus at the injection site, and skin biopsies revealed mild panniculitis with CD3(+) cells surrounding scanty residual tumor cells. There was a lim ited but significant peripheral monocytosis, No patient showed any inc rease in direct cytotoxic effector function against the immunizing cel l line, but 3 patients had a rise in the frequency of neuroblastoma-re active cytotoxic T lymphocyte precursor cells. One child had > 90% tum or response (PR), 7 had stable disease, and 4 had progressive disease in response to vaccine alone. Although these results offer some encour agement for the continued pursuit of allogeneic vaccine strategies in human cancer, the antitumor immune responses we observed are inferior to those obtained in an earlier immunization study using autologous ne uroblastoma cells. Hence, we suggest that this earlier approach remain s preferable, its difficulties notwithstanding.