Adecatumumab

Adecatumumab (Anti-Human EPCAM Recombinant Antibody; MT201) is a full human monoclonal antibody of the IgG1 isotype, targeting human EpCAM. Adecatumumab is expressed in almost all adenocarcinomas, and its activity is not dependent of K-Ras status[1][2].

Research Areas >> Cancer

Signaling Pathways >> Others >> Others

Human EPCAM[1]

Adecatumumab (4 μM; 18 h) shows diverse kinetic binding activities among human Adecatumumab and murine Adecatumumab in B16/EpCAM 3E3 cells[2]. Adecatumumab (0.1 ng/mL-0.1 mg/mL; 4 h) shows a dose-dependent Antibodies depend on cell-mediated cytotoxicity (ADCC) activity in natural killing (NK) cells[2].

Adecatumumab (300 μg/mouse; i.v. bolus injection; 3 times per week) inhibits tumor growth in B16/EpCAM xenograft tumor model in mice, both of human adecatumumab and mu-adecatumumab[2]. Both human adecatumumab and mu-adecatumumab (300 μg/mouse; i.v. bolus injection; single dose) exhibit a bi-exponential curve progression of serum concentration with an early distribution phase between 0 and 10 h and a terminal elimination phase[2]. Animal Model: Female immunocompetent C57BL/6 mice (6-10 weeks old) with B16/EpCAM (i.v.)[2] Dosage: 250 μg/mouse and 600 μg/mouse for human Adecatumumab; 125 μg/mouse and 300 μg/mouse for murine Adecatumumab Administration: 250 μg/mouse and 600 μg/mouse for human Adecatumumab; 125 μg/mouse and 300 μg/mouse for murine Adecatumumab Result: Both of them exhibited anti-tumor activity against B16/EpCAM cells in mice. Although human adecatumumab inhibited the size of tumor colonies mice, the number of colonies was only slightly reduced after treatment without significant difference. In contrast, mu-adecatumumab induced a highly significant reduction in the number of lung tumor colonies by >85%, and the few remaining tumor colonies were of very small size.

[1]. Kurtz JE, et al. Adecatumumab: an anti-EpCAM monoclonal antibody, from the bench to the bedside. Expert Opin Biol Ther. 2010 Jun;10(6):951-8.  

[2]. Lutterbuese P, et al. Exchanging human Fcgamma1 with murine Fcgamma2a highly potentiates anti-tumor activity of anti-EpCAM antibody adecatumumab in a syngeneic mouse lung metastasis model. Cancer Immunol Immunother. 2007 Apr;56(4):459-68.