In vitro and in vivo activity of MT201, a fully human monoclonal antibody for pancarcinoma treatment

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Item Type:	Article
Title:	In vitro and in vivo activity of MT201, a fully human monoclonal antibody for pancarcinoma treatment
Creators Name:	Naundorf, S., Preithner, S., Mayer, P., Lippold, S., Wolf, A., Hanakam, F., Fichtner, I., Kufer, P., Raum, T., Riethmueller, G., Baeuerle, P.A. and Dreier, T.
Abstract:	In our study, a novel, fully human, recombinant monoclonal antibody of the IgG1 isotype, called MT201, was characterized for its binding properties, complement-dependent (CDC) and antibody-dependent cellular cytotoxicity (ADCC), as well as for its in vivo antitumor activity in a nude mouse model. MT201 was found to bind its target, the epithelial cell adhesion molecule (Ep-CAM; also called 17-1A antigen, KSA, EGP-2, GA733-2), with low affinity in a range similar to that of the clinically validated, murine monoclonal IgG2a antibody edrecolomab (Panorex®). MT201 exhibited Ep-CAM-specific CDC with a potency similar to that of edrecolomab. However, the efficacy of ADCC of MT201, as mediated by human immune effector cells, was by 2 orders of magnitude higher than that of edrecolomab. Addition of human serum reduced the ADCC of MT201 while it essentially abolished ADCC of edrecolomab within the concentration range tested. In a nude mouse xenograft model, growth of tumors derived from the human colon carcinoma line HT-29 was significantly and comparably suppressed by MT201 and edrecolomab. The fully human nature and the improved ADCC of MT201 with human effector cells will make MT201 a promising candidate for the clinical development of a novel pan-carcinoma antibody that is superior to edrecolomab.
Keywords:	Ep-CAM, Edrecolomab, Monoclonal Antibody, Animals, Cricetinae, Mice
Source:	International Journal of Cancer
ISSN:	0020-7136
Publisher:	Wiley
Volume:	100
Number:	1
Page Range:	101-110
Date:	1 July 2002
Official Publication:	https://doi.org/10.1002/ijc.10443
PubMed:	View item in PubMed

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