Treatment of meningeal breast cancer xenografts in the rat using an anti-p185/HER2 antibody.
The metastatic spread of breast cancer to the leptomeninges (LM) is a painful, debilitating, and usually lethal condition. Current therapies are generally ineffective or extremely toxic. The current study evaluated monoclonal antibody therapy in an animal model of LM human breast cancer. Monoclonal antibody 4D5, which recognizes the extracellular domain of the HER2/neu receptor, was administered into the cerebrospinal fluid of athymic rats implanted with human breast cancer cell lines. Continuous intraventricular administration of 4D5 inhibited growth of SKBR3 cells that overexpress HER2/neu but not of MCF7 cells, which do not. Inhibition was dose-dependent, with higher doses of 4D5 producing an improved response. i.p. administration of cisplatin in addition to 4D5 did not improve results. Continuous administration of 4D5 into the lumbar, as opposed to the ventricular intrathecal space, was not therapeutically effective. Treatment with 4D5 did not result in outgrowth of cells lacking expression of the HER2/neu receptor. These results suggest that 4D5, administered regionally, may palliate LM metastases from HER2/neu-overexpressing breast carcinoma.
Bergman
I
I
Department of Pediatrics, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA.
Barmada
M A
MA
Griffin
J A
JA
Slamon
D J
DJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000134:cerebrospinal fluid / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D008577:Meningeal Neoplasms / Q000188:drug therapy* / Q000556:secondary; D009368:Neoplasm Transplantation; D051381:Rats; D011923:Rats, Nude; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D018719:Erb-b2 Receptor Tyrosine Kinases