IMMUNOMODULATORY EFFECTS OF HUMAN NEUROBLASTOMA-CELLS TRANSDUCED WITHA RETROVIRAL VECTOR ENCODING INTERLEUKIN-2

We have investigated whether retroviral mediated transfer of the IL-2 gene renders human neuroblastoma cells immunogenic, justifying their u se in a clinical tumor immunization study. Fourteen neuroblastoma cell lines were established from patients with disseminated neuroblastoma and transduced with the vector G1Ncvl2, which contains the neomycin ph osphotransferase gene and the cDNA of the human interleukin-2 gene. Cl ones secreting >150 pg/10(6) cells/24 h of IL-2 were selected for furt her study. Secretion of IL-2 was maintained for at least 3 weeks in no nselective media, implying that production of the cytokine would conti nue under in vivo conditions. Co-culture of IL-2 transduced cell lines with patient lymphocytes induced potent cytotoxic activity against bo th transduced and parental neuroblastoma cell lines. This activity was HLA unrestricted, and predominantly mediated by CD16+ or CD56+ and CD 8- lymphocytes. These data form the preclinical justification for our current immunization protocol for patients with relapsed or resistant neuroblastoma.