Oligo-clonal nanobodies as an innovative targeting agent for cancer therapy: New biology and novel targeting systems.
Variable heavy chain of HcAb (VHH), the smallest intact antibody fragment, possesses sub-nanomolar affinity to antigens. In spite of conventional antibodies, these fragments recognize concave and linear epitopes. VHHs are one the best weapon for targeted drug delivery in nanomedicine and biopharmaceutics. HER2 is overexpressed in 20-25% of breast and ovarian cancers. For many reasons, HER2 is a prominent target for drug delivery to breast tumor. In this study, we designed a robust prokaryotic expression system to express functional VHHs against HER2 receptor. This system showed high recombinant yields besides purified VHHs flow cytometry verified great capabilities of these molecules to pinpoint ecto-domain of HER2 receptor in MC4L2 HER2+ while insignificant non-specific binding to MC4L2 HER2-confirm nanobodies trivial cross-reaction. In the next step, we evaluated cooperative effect of four distinctive VHHs (oligoclonal VHHs) targeting different epitopes on HER2. As our result proved, using oligoclonal nanobodies as targeting moiety enhance targeting efficacy in comparison with monoclonal VHH.
Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address: Shahryar.khoshtinat@modares.ac.ir.
Shahryar Khoshtinat
SK
Nikkhoi
Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address: rahbarif@modares.ac.ir.
Fatemeh
F
Rahbarizadeh
School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran. Electronic address: d.ahmadvand@hotmail.com.
Davoud
D
Ahmadvand
D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D000939:Epitopes / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D061905:Single-Domain Antibodies / Q000494:pharmacology*
D000939:Epitopes; D018719:Erb-b2 Receptor Tyrosine Kinases; D061905:Single-Domain Antibodies; C508053:ERBB2 protein, human
Breast cancer; Cancer; Protein expression; Targeted drug delivery; VHH