A Macropinocytosis-Intensifying Albumin Domain-Based scFv Antibody and Its Conjugate Directed against K-Ras Mutant Pancreatic Cancer

Molecular Pharmaceutics
Xiao-Fei WangYong-Su Zhen

Abstract

Enhanced macropinocytosis has been found in K-Ras mutant pancreatic cancer cells, through which albumin can massively enter into the K-Ras-driven cancer cells, suggesting its role in serving as a macropinocytosis-intensifying drug delivery carrier. In the present study, a novel recombinant protein Fv-LDP-D3 and its reconstituted analogue Fv-LDP-D3-AE were designed and prepared. Fv is the fragment of an anti-EGFR antibody, D3 is the domain III of human serum albumin (HSA), LDP is the apoprotein of the antitumor antibiotic lidamycin (LDM), and AE is an extremely cytotoxic enediyne chromophore derived from LDM. As shown, the recombinant protein Fv-LDP-D3 presented intensive and selective binding capacity to pancreatic cancer cells and inhibited cell proliferation by blocking EGFR signaling. Moreover, Fv-LDP-D3 showed prominent tumor imaging in pancreatic carcinoma xenograft. The reconstituted, enediyne-integrated analogue Fv-LDP-D3-AE displayed highly potent cytotoxicity to pancreatic cancer cells through apoptosis induction and G2/M arrest. Fv-LDP-D3 and Fv-LDP-D3-AE markedly inhibited the tumor growth of the pancreatic carcinoma AsPC-1 xenograft. Study results indicated that the novel recombinant protein displays both EGFR-targe...Continue Reading

References

Nov 27, 2004·Molecular Therapy : the Journal of the American Society of Gene Therapy·Ikuhiko NakaseShiroh Futaki
Jun 28, 2008·Journal of Controlled Release : Official Journal of the Controlled Release Society·Felix Kratz
Apr 8, 2009·Proceedings of the American Thoracic Society·Gregory J RielyWilliam Pao
Aug 31, 2010·Protein Engineering, Design & Selection : PEDS·Vania E KenanovaAnna M Wu
Jan 5, 2012·Nature Communications·Jan Terje AndersenInger Sandlie
May 24, 2014·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yin XiangbaoFu Huaqun
Apr 13, 2015·EMBO Molecular Medicine·Hongsik LeeJunseo Oh
Mar 18, 2016·Journal of Cell Science·G Aaron HobbsKent L Rossman
Mar 25, 2016·Clinical and Translational Gastroenterology·Barbara BournetLouis Buscail
Sep 28, 2016·Frontiers in Physiology·Kevin D HaBin Liu
Jan 18, 2017·Cancer Letters·Janaiah KotaMurray Korc
Apr 11, 2017·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Jian XuYong-Su Zhen

❮ Previous
Next ❯

Citations

Dec 8, 2020·Scandinavian Journal of Gastroenterology·Carl AndreassonRoland Andersson
May 1, 2021·Antibody Therapeutics·Mahendra P Deonarain, Quinn Xue
Jul 21, 2021·International Journal of Biological Macromolecules·Hong-Yu TaoYong-Su Zhen
Jul 11, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Imke Rudnik-Jansen, Kenneth A Howard
Mar 27, 2019·Bioconjugate Chemistry·Qing LiM Jack Borrok

❮ Previous
Next ❯

Related Concepts

Related Feeds

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.