Asset

  • No.

    99

  • Asset Title

    FabRack Universal CAR-T

  • Organization

    City of Hope

  • Product Type

    Peptide

  • Therapeutic Area

    Oncology

  • Development Stage

    Hit To Lead or Lead Optimization

  • Technical Summary

    • Monoclonal antibodies (mAbs) have exceptional specificity and favorable pharmacology therefore, substantial efforts have been made to functionalize them, either with potent cytotoxins, biologics, radionuclides, or fluorescent groups for therapeutic benefit and/or use as theranostic agents.

     

    • To exploit the discovered meditope–Fab interaction as an alternative means to efficiently functionalize mAbs, inventors used insights from the structure to enhance the affinity and lifetime of the interaction by four orders of magnitude.

     

    • To further extend the lifetime of the complex, inventors created a mechanical bond by incorporating an azide on the meditope, threading the azide through the Fab, and using click chemistry to add a steric group. The mechanically interlocked, meditope–Fab complex retains antigen specificity and is capable of imaging tumors in mice.

     

    • These results indicate it is possible to “snap” functionality onto mAbs, opening the possibility of rapidly creating unique combinations of mAbs with an array of cytotoxins, biologics, and imaging agents.

     

  • Patent

    WO2019134001A1

  • Publication

    Mechanically interlocked functionalization of monoclonal antibodies, Nat Comm. (2018)
    Template-Catalyzed, Disulfide Conjugation of Monoclonal Antibodies Using a Natural Amino Acid Tag, Bioconj. Chem (2018)

  • Attachment

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