Identification of anti-ErbB2 dual variable domain immunoglobulin (DVD-Ig™) proteins with unique activities.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 24824849.
- Also identified by DOI 10.1371/journal.pone.0097292 and PMC identifier 4019538.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Inhibiting ErbB2 signaling with monoclonal antibodies (mAbs) or small molecules is an established therapeutic strategy in oncology. We have developed anti-ErbB2 Dual Variable Domain Immunoglobulin (DVD-Ig) proteins that capture the function of a combination of two anti-ErbB2 antibodies. In addition, some of the anti-ErbB2 DVD-Ig proteins gain the new functions of enhancing ErbB2 signaling and cell proliferation in N87 cells. We further found that two DVD-Ig proteins, DVD687 and DVD688, have two distinct mechanisms of actions in Calu-3 and N87 cells. DVD687 enhances cell cycle progression while DVD688 induces apoptosis in N87 cells. Using a half DVD687, we found that avidity may play a key role in the agonist activity of DVD687 in N87 cells.
Medical subject headings
- Antibodies, Monoclonal
- Immunoglobulins
- Erb-b2 Receptor Tyrosine Kinases
- Signal Transduction