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 painf ul, debilitating, and usually lethal condition. Current therapies are gener ally 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 rec eptor, was administered into the cerebrospinal fluid of athymic rats implan ted with human breast cancer cell lines. Continuous intraventricular admini stration of 4D5 inhibited growth of SKBR3 cells that overexpress HER2/neu b ut not of MCF7 cells, which do not. Inhibition was dose-dependent, with hig her doses of 4D5 producing an improved response. i.p. administration of cis platin in addition to 4D5 did not improve results, Continuous administratio n of 4D5 into the lumbar, as opposed to the ventricular intrathecal space, was not therapeutically effective. Treatment with 4D5 did not result in out growth of cells lacking expression of the HER2/neu receptor. These results suggest that 4D5, administered regionally, may palliate LM metastases from HER2/neu-over-expressing breast carcinoma.