Cancer Therapies Using Engineered Monomeric Fc Molecules

The National Cancer Institute, Nanobiology Program seeks parties interested in collaborative research to co-develop engineered molecules therapies.

Efforts to engineer antibody-based therapeutics, to date, have encountered technical limitations due to the relatively large fragment size and short fragment half-life. Antibody fragments are emerging as promising biopharmaceuticals because of their relatively small size and other unique properties. However, compared with full-size antibodies, these antibody fragments lack the ability to bind to some Fc receptor and have reduced half-lives.

NCI scientists have developed small (∼27 kDa) antibody fragments that are potentially useful for therapeutic development.  These are monomeric IgG fragment (mFc) compositions; they have long half-lives, are functional (pH dependent binders of neonatal Fc receptor - FcRn); soluble, and they express in E. coli efficiently.  The molecules may serve as a platform for development of engineered mFc-based antibodies and fusion proteins with therapeutic applications: the smaller size may allow for superior access to targets and tissues compared to full sized mAbs and larger fragment-based therapeutics, while also retaining important functional characteristics. The IgG Fc is a dimer of two constant domains (CH2-CH3 chains). The Fc has a long half-life, which makes it promising as a candidate for engineering antibody therapeutics.