Development and characterization of an IL-4-secreting human ovarian carcinoma cell line.
Human ovarian carcinoma cell lines were genetically engineered to secrete the cytokine interleukin-4 (IL-4) by retroviral-mediated gene transduction. These cells were transduced with the LXSN retroviral vector containing the human IL-4 gene and the neomycin resistance selection marker. Numerous IL-4-secreting clones were isolated from different papillary serous carcinoma cell lines, including SKOV-3, UCI-101, and UCI-107, and one clone derived from UCI-107 extensively characterized. This clone, termed UCI 107E IL-4 GS, was shown to constitutively express high levels of IL-4 (i.e., 900 to 1300 pg/ml/10(5) cells/48 hr) for over 35 passages and 6 months of study. Like the parental cell line (UCI-107), UCI 107E IL-4 GS cells expressed MHC class I and Her-2/neu surface antigens but did not express detectable MHC class II, ICAM 1, CA 125, or IL-4 receptors. No increase in expression of surface proteins was noted between parental and UCI 107E IL-4 GS. The morphology of this clone did not differ from that of the parental or LXSN vector control cells; however, parental cells had a faster growth rates than transductants. UCI 107E IL-4 GS was sensitive to gamma irradiation since as little as 2500 rad killed most of the cells within 10 days of irradiation. However, after irradiation, IL-4 secretion continued until about Day 8. The potential use of these IL-4-secreting ovarian carcinoma cells as vaccines for woman with advanced ovarian cancer will be discussed.
Santin
A D
AD
Department of Molecular Biology and Biochemistry, University of California, Irvine 92717, USA.
Ioli
G R
GR
Hiserodt
J C
JC
Rose
G S
GS
Graf
M R
MR
Tocco
L M
LM
Lander
J K
JK
Eck
L M
LM
Burger
R A
RA
DiSaia
P J
PJ
D000951:Antigens, Neoplasm / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis; D002455:Cell Division / Q000502:physiology; D002470:Cell Survival / Q000502:physiology / Q000528:radiation effects; D002999:Clone Cells; D018283:Cystadenocarcinoma, Papillary / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D004273:DNA, Neoplasm / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D005822:Genetic Vectors / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D007700:Kinetics; D010051:Ovarian Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D010957:Plasmids / Q000235:genetics; D012190:Retroviridae / Q000235:genetics; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured / Q000528:radiation effects; D014612:Vaccines / Q000235:genetics*
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D004273:DNA, Neoplasm; D004279:DNA, Viral; D015395:Histocompatibility Antigens Class I; D014612:Vaccines; D018799:Intercellular Adhesion Molecule-1; D015847:Interleukin-4