Anti-RELA monoclonal antibody, clone 38G0.H5

Peptide-based cancer therapy has been of great interest due to the unique advantages of peptides, such as their low MW, the ability to specifically target tumour cells, easily available and low toxicity in normal tissues. Therefore, identifying and synthesizing novel peptides could provide a promising option for cancer patients. The antitumour second generation peptide, CIGB-552 has been developed as a candidate for cancer therapy. Proteomic and genomic studies have identified the intracellular protein COMMD1 as the specific target of CIGB-552. This peptide penetrates to the inside tumour cells to induce the proteasomal degradation of RelA, causing the termination of NF-kappa B signalling. The antitumour activity of CIGB-552 has been validated in vitro in different human cancer cell lines, as well as in vivo in syngeneic and xenograft tumour mouse models and in dogs with different types of cancers. The aim of this review is to present and discuss the experimental data obtained on the action of CIGB-552, including its mechanism of action and its therapeutic potential in human chronic diseases. This peptide is already in phase I clinical trials as antineoplastic drug and has also possible application for other inflammatory and metabolic conditions.

The NF kappa B transcription factor family members RelA, p50, and cRel form homo- and heterodimers that are inhibited by I kappa B alpha, I kappa B beta, and I kappa B epsilon. These NF kappa B family members have diverse biological functions, and their expression profiles differ, leading to different concentrations in different tissue types. Here we present definitive biophysical measurements of the NF kappa B dimer affinities and inhibitor affinities to better understand dimer exchange and how the presence of inhibitors may alter the equilibrium concentrations of NF kappa B dimers in the cellular context. Fluorescence anisotropy binding experiments were performed at low concentrations to mimic intracellular concentrations. We report binding affinities much stronger than those that had been previously reported by non-equilibrium gel shift and analytical ultracentrifugation assays. The results reveal a wide range of NF kappa B dimer affinities and a strong preference of each I kappa B for a small subset of NF kappa B dimers. Once the preferred I kappa B is bound, dimer exchange no longer occurs over a period of days. A mathematical model of the cellular distribution of these canonical NF kappa B transcription factors based on the revised binding affinities recapitulates intracellular observations and provides simple, precise explanations for observed cellular phenomena.