Immunomodulatory effects of human neuroblastoma cells transduced with a retroviral vector encoding interleukin-2.
We have investigated whether retroviral mediated transfer of the IL-2 gene renders human neuroblastoma cells immunogenic, justifying their use 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 phosphotransferase gene and the cDNA of the human interleukin-2 gene. Clones secreting > 150 pg/10(6) cells/24 h of IL-2 were selected for further study. Secretion of IL-2 was maintained for at least 3 weeks in nonselective media, implying that production of the cytokine would continue under in vivo conditions. Co-culture of IL-2 transduced cell lines with patient lymphocytes induced potent cytotoxic activity against both transduced and parental neuroblastoma cell lines. This activity was HLA unrestricted, and predominantly mediated by CD16+ or CD56+ and CD8- lymphocytes. These data form the preclinical justification for our current immunization protocol for patients with relapsed or resistant neuroblastoma.
Leimig
T
T
Department of Hematology/Oncology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
Foreman
N
N
Rill
D
D
Coze
C
C
Holladay
M
M
Brenner
M
M
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D015703:Antigens, CD / Q000032:analysis; D018076:DNA, Complementary / Q000235:genetics; D017930:Genes, Reporter; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D019868:Kanamycin Kinase; D016131:Lymphocyte Subsets / Q000276:immunology; D009447:Neuroblastoma / Q000276:immunology / Q000473:pathology*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000096:biosynthesis / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012190:Retroviridae / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured; D014611:Vaccination
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018076:DNA, Complementary; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); D019868:Kanamycin Kinase