Neuroblastoma regression and immunity induced by transgenic expression of interleukin-12

Purpose: Interleukin-12 (IL-12) is a cytokine with potent antitumor effects . The authors sought to assess its capacity to increase tumor immunogenicit y when expressed by tumor cells in a murine model of neuroblastoma. Methods: Syngeneic A/J mice were inoculated subcutaneously with 2 x 10(6) c ells from a murine neuroblastoma-derived cell line (neuro-2a). In situ tran sduction of the neuroblastoma cells was achieved by intratumoral injection of an adenoviral vector encoding both subunits of the murine IL-12 heterodi mer. Growth of the IL-12 gene-modified tumor cells was compared with untrea ted neuro-2a cells. Tumor immunity was assessed by rechallenging mice that had rejected their tumor with unmodified neuroblastoma cells. The contribut ion of cytotoxic T lymphocytes (CTLs) was evaluated through cytotoxicity as says. Results: Eighteen (72%) of 25 tumor-bearing mice treated with the mIL-12 ad enoviral vector exhibited tumor regression, with 12 mice (48%) completely r ejecting their tumors over 2 to 3 weeks. None of the mice that had rejected their tumor and were rechallenged with unmodified neuro-2a cells subsequen tly developed new tumors. Pooled splenocytes from mice rejecting their tumo rs showed significant tumor killing (>20% cytolysis) in vitro in Cr-51 rele ase assays. Conclusions:Adenoviral-mediated IL-l 2 expression by tumor cells in a murin e neuroblastoma model produced a significant antitumor response. Most treat ed tumors demonstrated at least transient regression, whereas many complete ly regressed. Cured mice exhibited protective immunity and CTL activity aga inst the tumor. These data confirm the immunomodulatory efficacy of IL-12 a s part of a vaccine-based antineuroblastoma strategy. Copyright (C) 1999 by W.B. Saunders Company.