Recombinant-fully-human-antibody decorated highly-stable far-red AIEdots for in vivo HER-2 receptor-targeted imaging.

We developed highly bright and stable far-red emissive AIEdots by using a new kind of click-functional PEG grafted amphiphilic polymer to coat hydrophobic AIE-active polymers (PDFDP). Furthermore, an anti-HER2 recombinant fully human antibody was produced and conjugated on the AIEdots via metal-free click chemistry to fabricate in vivo tumor-targeting nanoprobes.

A dual-specific IGF-I/II human engineered antibody domain inhibits IGF signaling in breast cancer cells.

The insulin-like growth factors (IGFs), IGF-I and IGF-II, are essential for regulating cell growth, differentiation and metastasis of a broad range of malignancies. The IGF-I/II actions are mediated through the IGF receptor type 1 (IGF-1R) and the insulin receptor (IR), which are overexpressed in multiple types of tumors. Here, we have firstly identified a human engineered antibody domain (eAd) from a phage-displayed VH library. The eAd suppressed the signal transduction of IGF-1R mediated by exogenous IGF-I or IGF-II in breast cancer cell lines through neutralizing both IGF-I and IGF-II. It also significantly inhibited the growth of breast cancer cells. Therefore, the anti-IGF-I/II eAd offers an alternative approach to target both the IGF-1R signaling pathways through the inhibition of IGF-I/II.

N-terminal α-amino group modification of antibodies using a site-selective click chemistry method.

Site-specific conjugation of small molecules to antibody molecules is a promising strategy for generation of antibody-drug conjugates. In this report, we describe the successful synthesis of a novel bifunctional molecule, 6-(azidomethyl)-2-pyridinecarboxyaldehyde (6-AM-2-PCA), which was used for conjugation of small molecules to peptides and antibodies. We demonstrated that 6-AM-2-PCA selectively reacted with N-terminal amino groups of peptides and antibodies. In addition, the azide group of 6-AM-2-PCA enabled copper-free click chemistry coupling with dibenzocyclooctyne-containing reagents. Bifunctional 6-AM-2-PCA mediated site-specific conjugation without requiring genetic engineering of peptides or antibodies. A key advantage of 6-AM-2-PCA as a conjugation reagent is its ability to modify proteins in a single step under physiological conditions that are sufficiently moderate to retain protein function. Therefore, this new click chemistry-based method could be a useful complement to other conjugation methods.

Generation of Bispecific Antibodies by Fc Heterodimerization and their Application.

Bispecific antibodies with binding specificities for two different antigens have prompted a lot of interest into their development and application. Currently, more than ten bispecific antibodies have been clinically validated for the treatment of various diseases, including cancers and inflammatory diseases. Intensive studies in antibody engineering drive the generation of different bispecific antibody formats that differ in size and shape. However, the most prominent formats, such as IgG-single-chain (sc) Fv or dual-variable domain (DVD) IgG, deviating from the natural IgG structure, may lead to manufacturing difficulties or increase the potential risk of immunogenicity. Thus, the recent efforts focus on the development of bispecific antibodies by Fc heterodimerization that maintain the native structure of the antibody IgG molecule. This review summarizes the various techniques and methods to generate bispecific antibody molecules with Fc heterodimerization, and discusses perspectives of their application.