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>Neoplasia. 2003 Nov-Dec;5(6):489-94. Related Articles,
ING-1(heMAb), a monoclonal antibody to epithelial cell adhesion molecule, inhibits tumor metastases in a murine cancer model.
Ruan HH, Scott KR, Bautista E, Ammons WS.
Department of Pharmacology, XOMA (US) LLC, Berkeley, CA 94710, USA. ruan@xoma.com
ING-1(heMAb), a human-engineered monoclonal antibody (MAb) that specifically targets the epithelial cell adhesion molecule (Ep-CAM), kills adenocarcinoma cells in vitro and inhibits tumor growth in vivo. In the current study, we evaluated the efficacy of ING-1(heMAb) in a murine model of cancer metastases. Mice received intravenous dosing of 1 mg/kg ING-1(heMAb), twice a week, starting on day 2 or day 5. A negative control group received 1 mg/kg human immunoglobulin G with the same dose frequency starting on day 2. A positive control group received weekly 100 mg/kg 5-flurouracil/leucovorin starting on day 2. ING-1(heMAb)/day 2 treatment significantly reduced both the number of visible tumor nodules in body cavities (P <.01) and the number of metastases on lung surfaces (P <.005). The treatment also resulted in a 91% reduction of micrometastases in lung tissues (P <.0001). Delaying ING-1(heMAb) treatment until day 5 caused 54% reduction in micrometastases (P <.005). Our results indicate that a number of parameters, including treatment starting day, dose level, and dose frequency, are critical in achieving the optimal efficacy of ING-1(heMAb). We conclude that ING-1(heMAb) effectively reduced tumor metastases in a murine cancer model. Immunotherapy with ING-1(heMAb) may be beneficial in treating human metastatic diseases |
