The effect of antibodies and immunotoxins reactive with HER-2/neu on growth of ovarian and breast cancer cell lines.
OBJECTIVE
Because HER-2/neu is overexpressed in one third of breast and ovarian cancers, we examined the effect of unconjugated monoclonal antibodies (ID-5, PB-3, TA-1) and an immunotoxin (TA-1-ricin) reactive with this protooncogene on the growth of breast and ovarian cancer cell lines.


METHODS
The tritiated thymidine incorporation assay was used to examine the effect of unconjugated antibodies on proliferation. A limiting dilution clonogenic assay was used to assess the effect of immunotoxin on cellular cytotoxicity.


RESULTS
Scatchard analysis revealed that OVCA 420, OVCA 429, OVCA 432, and OVCA 433 cells had approximately 10(4) HER-2/neu receptors per cell, whereas the SKOv3 and SKBr3 cell lines expressed 10(5) and 10(6) receptors per cell, respectively. Monoclonal antibody ID-5 caused significant inhibition of tritiated thymidine incorporation in SKBr3, SKOv3, and OVCA 420 cells (p < 0.002). The TA-1-rich immunotoxin significantly inhibited the clonogenic growth of only SKBr3 and SKOv3 cells.


CONCLUSIONS
HER-2/neu may be a useful target for immunotherapy with unconjugated antibodies and immunotoxins in ovarian and breast cancers that overexpress this protooncogene.
Rodríguez
G C
GC
Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC 27710.
Boente
M P
MP
Berchuck
A
A
Whitaker
R S
RS
O'Briant
K C
KC
Xu
F
F
Bast
R C
RC
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000992:Antitoxins / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D066246:ErbB Receptors; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007167:Immunotherapy; D010051:Ovarian Neoplasms / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000187:drug effects*; D011519:Proto-Oncogenes / Q000187:drug effects*; D012276:Ricin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000992:Antitoxins; D011518:Proto-Oncogene Proteins; D012276:Ricin; D066246:ErbB Receptors