The first tyrosine kinase receptor, epidermal growth factor receptor (EGFR or HER1) was associated with cell growth and human tumors. Several small molecule and IgG antibodies targeting EGFR have been approved for the inhibition of tumor growth and apoptosis.
Single domain Antibody (SdAb), or heavy-chain variable (VHH), abbreviately known as nanobody, has several unique characteristics in comparison with conventional antibodies, including low molecule weight, high solubility, high stability, and high affinity. To date, several nanobodies, including αEGFR-αEGFR-Alb、8B6、7D12、7C12、EG2、9G8、B39、EGa1、D10, targeting EGFR extracellular domain have been developed.
A bivalent anti-EGFR nanobody, αEGFR-αEGFR-Alb, can bind to albumin and improve stability, tumor uptake, and biodistribution. The results of affinity evaluation, inhibitions of tumor cell growth, and phosphorylation pathways indicated that the order of nanobodies assembly plays an important role in the design of bivalent nanobodies. However, labeled mono-valent nanobodies such as 8B6, 7D12, 7C12, EG2, 9G8, B39, EGa1, and D10, are currently in preclinical studies and developed as imaging tools.
One of the main challenges for the radiopharmaceutical use of VHH is its high kidney uptake. Renal reabsorption of peptide-based radiopharmaceuticals can be reduced by several strategies, including engineering physicochemical characteristics of the tracer (i.e. glycosylation or PEGylation), augmenting the negative charges of the moiety, introducing a brush border enzyme-cleavable linker among the nanobody and radionuclide carrier agent, as well as injection of cationic amino acids (i.e. lysine, arginine) and/or gelatin-based plasma expanders (i.e. gelofusin).
Yaohai Bio-Pharma Offers One-Stop CDMO Solution for VHH/ sdAb
Anti-EGFR VHH In Development
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Anti-EGFR VHH
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Expression System
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Radiolabel
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8B6
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Escherichia coli (E. coli) TG1
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99mTc
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7D12
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E.coli TG1, E. coli BirA, fungal
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99mTc, 68Ga, 89Zr, IRDye800CW, QD
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7C12
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E.coli, E.coli Shuffle
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99mTc
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EG2
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E. coli BL21, E.coli (TG1), E.coli Shuffle, HEK293
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99mTc, QD
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B39
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E. coli BL21 (DE3)
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Nanocrystal
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EGa1
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E. coli BL21
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Tb-QD
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EgB4
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E. coli,
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Tb-QD
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D10
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E. coli BL21 (DE3), E.coli (TG1)
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99mTc
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OA-cb6
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E.coli TG1
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99mTc
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Anti-EGFR
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Pending update
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iRGD-DTPA-Gd
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Reference:
[1] Sharifi J, Khirehgesh MR, Safari F, Akbari B. EGFR and anti-EGFR nanobodies: review and update. J Drug Target. 2021 Apr;29(4):387-402. doi: 10.1080/1061186X.2020.1853756.
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