Enzyme-Mediated Modification of Single-Domain Antibodies for Imaging Modalities with Different Characteristics

Details

• Alternative Title:
  Angew Chem Int Ed Engl
• Personal Author:
  Rashidian, Mohammad ; Wang, Lu ; Edens, Jerre G. ; Jacobsen, Johanne T. ; Hossain, Intekhab ; Wang, Qifan ; Victora, Gabriel D. ; Vasdev, Neil ; Ploegh, Hidde ; Liang, Steven H.
• Description:
  Antibodies are currently the fastest-growing class of therapeutics. Although naked antibodies have proven valuable as pharmaceutical agents, they have some limitations, such as low tissue penetration and a long circulatory half-life. They have been conjugated to toxic payloads, PEGs, or radioisotopes to increase and optimize their therapeutic efficacy. Although nonspecific conjugation is suitable for most in vitro applications, it has become evident that site specifically modified antibodies may have advantages for in vivo applications. Herein we describe a novel approach in which the antibody fragment is tagged with two handles: one for the introduction of a fluorophore or (18)F isotope, and the second for further modification of the fragment with a PEG moiety or a second antibody fragment to tune its circulatory half-life or its avidity. Such constructs, which recognize Class II MHC products and CD11b, showed high avidity and specificity. They were used to image cancers and could detect small tumors.
• Subjects:
  Animals Article Cells, Cultured Dimerization Enzymes Half-Life Histocompatibility Antigens Class II Isotopic Labeling Melanoma, Experimental Mice Molecular Imaging PEGylation Positron Emission Tomography Single-domain Antibodies

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• Source:
  Angew Chem Int Ed Engl. 55(2):528-533
• Pubmed ID:
  26630549
• Pubmed Central ID:
  PMC4718774
• Document Type:
  Journal Article
• Funding:
  DP1 GM106409/GM/NIGMS NIH HHS/United States ; DP1-GM106409-03/DP/NCCDPHP CDC HHS/United States ; K01 DA038000/DA/NIDA NIH HHS/United States ; R01-AI087879-06/AI/NIAID NIH HHS/United States ; R01-GM100518-04/GM/NIGMS NIH HHS/United States ; R21 AI117373/AI/NIAID NIH HHS/United States ; R01 AI087879/AI/NIAID NIH HHS/United States ; R01 GM100518/GM/NIGMS NIH HHS/United States
• Volume:
  55
• Issue:
  2
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:11f0f36121fc99e202a2c7ef6bdf48cae123107d4be1638e4cfecf627537d943
• Download URL:
  https://stacks.cdc.gov/view/cdc/39431/cdc_39431_DS1.pdf
• File Type:
  [PDF - 1.79 MB ]