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Pernille Tofteng Shelton
Identification of Long Acting, GIP/GLP-1 Dual Acting Peptide Hormones
Zealand Pharma, Denmark
Development Of Liposomal Formulations For Intracellular Delivery Of Therapeutic Peptides
We have created and established a pipeline/ portfolio of validated B-cell peptide vaccines (HER-2, HER-3, HER-1, VEGF, IGF-1R and PD-1) against multiple receptor tyrosine kinases (RTK’s) to expedite the development of new paradigm shifting cancer immune-therapies.
We have translated two HER-2 B-cell epitopes peptide vaccines comprising epitopes designed to mimic the trastuzumab and pertuzumab binding epitopes to the clinic in an NCI-funded and FDA approved Phase 1/2b trial (NCT01376505). This presentation will detail our clinical trial and basic studies based on the development of combinatorial immunotherapeutic strategies that act synergistically to enhance immune-mediated tumor killing aimed at addressing mechanisms of tumor resistance for several tumor types.
Despite numerous intracellular therapeutic opportunities, less than 10% of peptides entering clinical trials have intracellular targets, due to inherent limitations such as poor cellular penetration and lysosomal degradation. With several formulations already on the market, liposomes have emerged as leading candidates for drug delivery, thanks to their versatility in terms of API formulation and therapeutic applications. Using a microfluidics platform, we developed several liposomal formulations of therapeutic peptides and investigated their intracellular entry. We demonstrated the possibility to efficiently load therapeutic peptides into liposomes, allowing effective delivery to tumor cells.
Peptides hold great potential as anticancer agents. However, a major challenge impeding the widespread use of peptides is their poor pharmacokinetic profile, due to short circulation half-life. In this talk I will discuss our effort in developing a fundamentally new approach for enhancing the circulation half-life of peptides without affecting its biological potency.
With the main goal of finding a green solvent that could be used in the large scale manufacture of peptide be the SPPS methodology. A set of candidate green solvents were tested for their feasibility of replacing reprotoxic DMF, our results indicates that N-Butylpyrrolidone (NBP) can be used as a green solvent for SPPS. In this presentation I will show our results and share our view for further development in the direction of a greener peptide synthesis.