Chapter 6: Overall discussion, future directions and concluding remarks
6.3 Concluding Remarks
While these studies have been carried out with the intention of designing an optimized HER2/neu targeting SPIO NP, the core findings of the studies truly lend themselves to the design and optimization of any nanoparticle platform targeted towards any receptor of interest. We have shown that the EPL-Click conjugation strategy easily extends to both classic and novel nanoparticle platforms. Additionally, we have shown that the EPL-Click system is applicable for any affinity ligand that can be bacterially expressed. With the ever-growing libraries of phage- and alternative scaffold-derived affinity ligands, it is expected that the utility of the EPL-Click system will extend to most any system or pathology of interest.
6.4 References
1. Garanger, E.; Blois, J.; Hilderbrand, S. A.; Shao, F.; Josephson, L., Divergent oriented synthesis for the design of reagents for protein conjugation. J Comb Chem 2010,
12, (1), 57-64.
2. Garanger, E.; Weissleder, R.; Josephson, L., A multifunctional single-attachment- point reagent for controlled protein biotinylation. Bioconjug Chem 2009, 20, (1), 170-3. 3. Helmick, L.; Antunez de Mayolo, A.; Zhang, Y.; Cheng, C. M.; Watkins, S. C.; Wu, C.; LeDuc, P. R., Spatiotemporal response of living cell structures in Dictyostelium discoideum with semiconductor quantum dots. Nano Lett 2008, 8, (5), 1303-8.
183 4. Heldt, C. L.; Gurgel, P. V.; Jaykus, L. A.; Carbonell, R. G., Influence of peptide ligand surface density and ethylene oxide spacer arm on the capture of porcine
parvovirus. Biotechnol Prog 2009, 25, (5), 1411-8.
5. Hellman, P.; Andersson, L.; Eriksson, H., Ligand surface density is important for efficient capture of immunoglobulin and phosphatidylcholine coated particles by human peripheral dendritic cells. Cell Immunol 2009, 258, (2), 123-30.
6. Rhodes, A., Developing a cell line standard for HER2/neu. Cancer Biomark 2005,
1, (4-5), 229-32.
7. Park, B. W.; Zhang, H. T.; Wu, C.; Berezov, A.; Zhang, X.; Dua, R.; Wang, Q.; Kao, G.; O'Rourke, D. M.; Greene, M. I.; Murali, R., Rationally designed anti-HER2/neu peptide mimetic disables P185HER2/neu tyrosine kinases in vitro and in vivo. Nat Biotechnol 2000, 18, (2), 194-8.
8. Weisser, N. E.; Hall, J. C., Applications of single-chain variable fragment antibodies in therapeutics and diagnostics. Biotechnol Adv 2009, 27, (4), 502-20. 9. Orlova, A.; Magnusson, M.; Eriksson, T. L.; Nilsson, M.; Larsson, B.; Hoiden- Guthenberg, I.; Widstrom, C.; Carlsson, J.; Tolmachev, V.; Stahl, S.; Nilsson, F. Y., Tumor imaging using a picomolar affinity HER2 binding affibody molecule. Cancer Res
2006, 66, (8), 4339-48.
10. Wang, S.; Zheng, C.; Liu, Y.; Zheng, H.; Wang, Z., Construction of multiform scFv antibodies using linker peptide. J Genet Genomics 2008, 35, (5), 313-6.
11. Depetris, M.; Casalis, P.; Kratje, R.; Etcheverrigaray, M.; Oggero, M., A scFv antibody fragment as a therapeutic candidate to neutralize a broad diversity of human IFN-alpha subtypes. J Immunol Methods 2008, 334, (1-2), 104-13.
184 12. Liu, M.; Wang, X.; Yin, C.; Zhang, Z.; Lin, Q.; Zhen, Y.; Huang, H., A novel bivalent single-chain variable fragment (scFV) inhibits the action of tumour necrosis factor alpha. Biotechnol Appl Biochem 2008, 50, (Pt 4), 173-9.
13. Shi, M.; Zhang, L.; Gu, H. T.; Jiang, F. Q.; Qian, L.; Yu, M.; Chen, G. J.; Luo, Q.; Shen, B. F.; Guo, N., Efficient growth inhibition of ErbB2-overexpressing tumor cells by anti-ErbB2 ScFv-Fc-IL-2 fusion protein in vitro and in vivo. Acta Pharmacol Sin
2007, 28, (10), 1611-20.
14. Park, K. J.; Lee, S. H.; Kim, T. I.; Lee, H. W.; Lee, C. H.; Kim, E. H.; Jang, J. Y.; Choi, K. S.; Kwon, M. H.; Kim, Y. S., A human scFv antibody against TRAIL receptor 2 induces autophagic cell death in both TRAIL-sensitive and TRAIL-resistant cancer cells.
Cancer Res 2007, 67, (15), 7327-34.
15. Caravella, J.; Lugovskoy, A., Design of next-generation protein therapeutics.
Curr Opin Chem Biol 2010, 14, (4), 520-8.
16. Schlapschy, M.; Grimm, S.; Skerra, A., A system for concomitant overexpression of four periplasmic folding catalysts to improve secretory protein production in
Escherichia coli. Protein Eng Des Sel 2006, 19, (8), 385-90.
17. King, C. R.; Fischer, P. H.; Rando, R. F.; Pastan, I., The performance of
e23(Fv)PEs, recombinant toxins targeting the erbB-2 protein. Semin Cancer Biol 1996, 7, (2), 79-86.
18. Adams, G. P.; Schier, R.; McCall, A. M.; Crawford, R. S.; Wolf, E. J.; Weiner, L. M.; Marks, J. D., Prolonged in vivo tumour retention of a human diabody targeting the extracellular domain of human HER2/neu. Br J Cancer 1998, 77, (9), 1405-12.
185 19. Maiti, B.; Shetty, M.; Shekar, M.; Karunasagar, I., Recombinant outer membrane protein A (OmpA) of Edwardsiella tarda, a potential vaccine candidate for fish, common carp. Microbiol Res, 2011, [EPub].
20. Bisi, D. C.; Lampe, D. J., Secretion of Anti-Plasmodium Effector Proteins from a Natural Isolate Pantoea Agglomerans Using Pelb and Hlya Secretion Signals. Appl Environ Microbiol, 2011 Jul;77(13):4669-75.
21. Orr-Weaver, T. L.; Szostak, J. W.; Rothstein, R. J., Yeast transformation: a model system for the study of recombination. Proc Natl Acad Sci U S A 1981, 78, (10), 6354-8. 22. Dorr, R. T., Clinical properties of yeast-derived versus Escherichia coli-derived granulocyte-macrophage colony-stimulating factor. Clin Ther 1993, 15, (1), 19-29; discussion 18.
23. Hamilton, S. R.; Bobrowicz, P.; Bobrowicz, B.; Davidson, R. C.; Li, H.; Mitchell, T.; Nett, J. H.; Rausch, S.; Stadheim, T. A.; Wischnewski, H.; Wildt, S.; Gerngross, T. U., Production of complex human glycoproteins in yeast. Science 2003, 301, (5637), 1244-6.
24. Rudolph, D.; Srinivasan, S.; Durham, D. R.; Heifetz, A., Expression of Recominant Proteins in Yeast. In Advanstar Communications, Inc.: 2006; Vol. 201. 25. Laboratory, P. N. N., Yeast Display scFv Antibody Library User Manual. In.