Development and characterization of an interleukin-2-transduced human ovarian carcinoma tumor vaccine not expressing major histocompatibility complex molecules.
OBJECTIVE
We initiated studies to develop cytokine-secreting human ovarian carcinoma cells for the purpose of using these cells as vaccines for the treatment of advanced epithelial ovarian cancer.


METHODS
A human ovarian carcinoma cell line (UCI-107) was genetically engineered to secrete the cytokine interleukin-2 by retroviral-mediated gene transduction.


RESULTS
One clone, termed UCI-107A IL-2 AS, constitutively secreted high levels of interleukin-2 (i.e., 2000 to 2300 pg/ml/10(5) cells per 48 hours) for > 55 passages and 8 months of study. Unlike parental- and vector-transduced cells, UCI-107A IL-2 AS cells were aneuploid and failed to express major histocompatibility complex class I and HER2/neu surface antigens. UCI-107A IL-2 AS cells were highly resistant to killing by gamma irradiation and continued to produce high levels of interleukin-2 even after irradiation with 10,000 cGy. Balb/C nude mice injected intraperitoneally with UCI 107-A IL-2 AS cells survived significantly longer than control animals, with 25% of the animals totally rejecting their tumors. UCI-107A IL-2 AS was totally resistant to killing by fresh allogeneic peripheral blood lymphocytes in four hour chromium 51 release assays but induced high levels of killing in 72-hour long-term cytotoxic assays.


CONCLUSIONS
The potential use of these interleukin-2-secreting ovarian carcinoma cells as vaccines for women with advance ovarian cancer will be discussed.
Santin
A D
AD
Department of Molecular Biology and Biochemistry, University of California, Irvine 92717-3900, USA.
Ioli
G R
GR
Hiserodt
J C
JC
Manetta
A
A
Pecorelli
S
S
DiSaia
P J
PJ
Granger
G A
GA
D000231:Adenocarcinoma, Papillary / Q000276:immunology; D000818:Animals; D003602:Cytotoxicity, Immunologic; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000032:analysis*; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000517:prevention & control*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D014162:Transfection; D014407:Tumor Cells, Cultured; D014612:Vaccines
D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; D018719:Erb-b2 Receptor Tyrosine Kinases; D014612:Vaccines