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Immunomodulatory effects of human neuroblastoma cells transduced with a retroviral vector encoding interleukin-2.
- Source :
-
Cancer gene therapy [Cancer Gene Ther] 1994 Dec; Vol. 1 (4), pp. 253-8. - Publication Year :
- 1994
-
Abstract
- 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.
- Subjects :
- Antibodies, Monoclonal immunology
Antibodies, Monoclonal pharmacology
Antigens, CD analysis
DNA, Complementary genetics
Genes, Reporter
Humans
Immunotherapy
Interleukin-2 immunology
Interleukin-2 metabolism
Kanamycin Kinase
Lymphocyte Subsets immunology
Neuroblastoma immunology
Phosphotransferases (Alcohol Group Acceptor) biosynthesis
Phosphotransferases (Alcohol Group Acceptor) genetics
Recombinant Fusion Proteins biosynthesis
Transfection
Tumor Cells, Cultured
Vaccination
Genetic Vectors genetics
Interleukin-2 genetics
Neuroblastoma pathology
Retroviridae genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0929-1903
- Volume :
- 1
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Cancer gene therapy
- Publication Type :
- Academic Journal
- Accession number :
- 7627815