RG7116, a therapeutic antibody that binds the inactive HER3 receptor and is optimized for immune effector activation.

The EGF receptor (EGFR) HER3 is emerging as an attractive cancer therapeutic target due to its central position in the HER receptor signaling network. HER3 amplifies phosphoinositide 3-kinase (PI3K)-driven tumorigenesis and its upregulation in response to other anti-HER therapies has been implicated in resistance to them. Here, we report the development and characterization of RG7116, a novel anti-HER3 monoclonal antibody (mAb) designed to block HER3 activation, downregulate HER3, and mediate enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) via glycoengineering of the Fc moiety.

Development of tetravalent IgG1 dual targeting IGF-1R-EGFR antibodies with potent tumor inhibition.

In this study we present novel bispecific antibodies that simultaneously target the insulin-like growth factor receptor type I (IGF-1R) and epidermal growth factor receptor (EGFR). For this purpose disulfide stabilized scFv domains of the EGFR/ADCC antibody GA201 were fused via serine-glycine connectors to the C-terminus of the heavy (XGFR2) or light chain (XGFR4), or the N-termini of the light (XGFR5) or heavy chain (XGFR3) of the IGF-1R antibody R1507 as parental IgG1 antibody. The resulting bispecific IGF-1R-EGFR antibodies XGFR2, XGFR3 and XGFR4 were successfully generated with yields and stability comparable to conventional IgG1 antibodies.

Fibroblast remodeling of adsorbed collagen type IV is altered in contact with cancer cells.

A series of co-culture experiments between fibroblasts and H-460 human lung carcinoma cells were performed to learn more about the fate of adsorbed type IV collagen (Coll IV). Fibroblasts were able to spatially rearrange Coll IV in a specific linear pattern, similar but not identical to the fibronectin (FN) fibrils. Coll IV partly co-aligns with fibroblast actin cytoskeleton and transiently co-localize with FN, as well as with beta1 and alpha2 integrin clusters, suggesting a cell-dependent process.

Identification of genes associated with enhanced metastasis of a large cell lung carcinoma cell line.

We have compared the transcriptional profile of large cell lung tumor cell lines NIH-H460 and H460-M making use of the Affymetrix GeneChip system. H460-M is derived from NIH-H460 and displays enhanced experimental and spontaneous metastasis in nude mice. Out of the 12,600 genes investigated, 73 (0.

Serum-free cultured keratinocytes fail to organize fibronectin matrix and possess different distribution of beta-1 integrins.

The development of serum free medium formulation for culturing keratinocytes was a breakthrough in achieving a high number of epidermal cells for experimental and therapeutic studies, in particular to support the wound healing process. It is not clear, however, if switching the cells to highly proliferative phenotype may reflect change in other cellular functions important for the wound repair as their adhesive interactions with the extracellular matrix components. Remodelling of the extracellular matrix, particularly of fibronectin plays an essential role for guiding the cells during wound healing.