Sustained cytokine production and immunophenotypic changes in human neuroblastoma cell lines transduced with a human gamma interferon vector.
The majority of human neuroblastomas express low to undetectable levels of major histocompatibility complex (MHC) class I and II antigens (MHC-I and -II). We studied the effects of gamma interferon (gamma-IFN) transduction on expression of these antigens in six human neuroblastoma cell lines with and without genomic amplification of the N-myc oncogene. All six were stably transduced with an MoMLV-based gamma-IFN retroviral vector (DAh gamma-IFN). G418-resistant cells were assayed for MHC-I, MHC-II, B7-1, and neuroblastoma-associated antigen expression, as well as for gamma-IFN levels in cell culture supernatants. Sustained gamma-IFN production, 2 to > 1000 units/10(6) cells/d, was attained for five of six transduced cell lines and persisted for up to 9 months. This resulted in marked upregulation of MHC-I and MHC-II expression in LA-N-1, LA-N-6, and CHLA-127 cells and moderate upregulation in SK-N-Fi and SK-N-AS cells. One cell line (LA-N-1) had marked induction of MHC-I and MHC-II despite marginal levels of gamma-IFN production. Expression of CD28 ligand B7-1 (as determined by BB1 antibody) remained unchanged in all gamma-IFN-transduced cell lines tested. Expression of several neuroblastoma-associated antigens (NKH1A, 126-4, HSAN 1.2, HNK, 459, and 390) was upregulated in some of the gamma-IFN-transduced cell lines. These results demonstrate that preparation of gamma-IFN expressing neuroblastoma cells for immunotherapeutic purposes is feasible and that gamma-IFN transduction results in phenotypic changes that may improve immunogenicity of human neuroblastoma cells.
UCLA Department of Medicine 90024-1678, USA.
K
K
Uçar
R C
RC
Seeger
P M
PM
Challita
C T
CT
Watanabe
T L
TL
Yen
J P
JP
Morgan
R
R
Amado
E
E
Chou
T
T
McCallister
J R
JR
Barber
D018122:B7-1 Antigen / Q000378:metabolism; D018106:CD28 Antigens / Q000378:metabolism; D018959:CD57 Antigens / Q000378:metabolism; D005822:Genetic Vectors; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D006801:Humans; D016130:Immunophenotyping; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics*; D009447:Neuroblastoma / Q000276:immunology* / Q000473:pathology; D010641:Phenotype; D011836:Radiation Tolerance; D012190:Retroviridae / Q000235:genetics; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured
D018122:B7-1 Antigen; D018106:CD28 Antigens; D018959:CD57 Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma