targeting intracellular proteins, page-6

Tony,
Interesting article in FierceBiotech, covering a new nanoparticle candidate in cancer research. Interesting for two reasons;

1. We have been discussing nanoparticles, in particular the Centyrin nanoparticle.
2. The research covers how "overall, the two-drug approach shows to increase the efficiency of the treatment, resulting in a 5.9-fold increase in cytotoxicity".

The reference to the increase in cytotoxcity or the improvement in efficiency may be applicable in the context of the Janssen and Phylogica collaboration and the current expanded stage re: capability of the CPPs to function within the cell.

Assuming the Janssen therapeutic cargo is a toxic cancer killer carried by a bi-specific Centyrin nanoparticle, how does the endosomal escape peptide (EEP) improve the level of cytotoxicity in say a Xenograft model.

Will the EEP increase the level of cytotoxicity or have no effect compared to the Centyrin acting alone. If there is an effect will it be a 1, 2 or 5 fold increase! Could it be a 10 fold increase? What is the number which will put ink to the licensing agreement?

There is an interesting reference in the Abstract which is linked to the FierceBiotech article;

"The parallel activity of TRAIL and Dox show synergistic anticancer efficacy."

The phrase 'synergistic anticancer efficacy' is worth noting. Remember how Phylogica have selected a series of cell penetrating peptides that bind with Fibronectin. In fact, the binding is so exquisite that Fibronectin actually enhances delivery. Recall also that Centyrin is an Alternative Scaffold designed from the Fibronectin Type 111 (FN3) domain. The hope is that the EEP will not only improve the efficiency of release of the cargo but that it will create a powerful synergy of action.