The Generation and Preclinical Evaluation of Multimeric Anti-Her-2 Antibodies
Abstract
We have generated a panel of 100 anti-Her-2 MAbs and have characterized them with regard to isotype, epitope recognition and ability to signal apoptosis in Her-2-overexpressing breast cancer cell lines. Twelve of these MAbs, recognizing nine different epitopes on the Her-2 molecule, negatively signal Her-2-overexpressing tumor cells. In parallel work which we are carrying out using MAbs against human lymphoma cells, we have observed that chemically prepared tumor-reactive MAb homodimers (IgG-IgG) of MAbs induce significantly more growth arrest and death than their monomeric (IgG) counterparts (11), probably because of hypercrosslinking (12). In our original application, we proposed evaluating the antitumor activity of our best 10 anti-Her-2 dimers. In the first six months of the project, we prepared IgG homodimers of representative MAbs recognizing the nine different epitopes on the Her-2 molecule. These homodimers were evaluated for their ability to induce apoptosis in Her-2-overexpressing human breast cancer cell lines. Based on these studies we choose three MAbs for follow-up studies. At this time, we have designed and are in the process of expressing three different recombinant homodimeric constructs with the Fv regions of these three MAbs.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2000
- Accession Number
- ADA385556
Entities
People
- Ellen S. Vitetta
Organizations
- University of Texas Southwestern Medical Center