In vitro and in vivo activity of MT201, a fully human monoclonal antibody for pancarcinoma treatment.
Int J Cancer
; 100(1): 101-10, 2002 Jul 01.
Article
in En
| MEDLINE
| ID: mdl-12115595
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(R)). 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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cell Adhesion Molecules
/
Antibodies, Monoclonal
/
Antigens, Neoplasm
/
Neoplasms
Limits:
Animals
/
Humans
Language:
En
Journal:
Int J Cancer
Year:
2002
Document type:
Article
Affiliation country:
Germany