Asset

  • No.

    103

  • Asset Title

    Engineered PSCA antibody for Targeted Radiotherapy

  • Organization

    City of Hope

  • Product Type

    Antibody

  • Therapeutic Area

    Oncology

  • Development Stage

    Hit To Lead or Lead Optimization

  • Technical Summary

    Intact Antibodies and Engineered Fragments 

    • Protein engineering offers extensive control over biological properties such as PK and organ of clearance 

    • Critical for efficacious delivery of therapeutic radionuclides 

     

    PET imaging to evaluate tumor targeting and clearance 

    • MicroPET imaging in xenograft-bearing mice using 124I-labeled antibodies and fragments 

    • Requires up to a week using intact antibodies 

    • 20-120 h for scFv-Fc

    • 20 h (minibody) or 4 h (diabody) for smaller fragments 

     

    ScFv-Fc fragments with tailored PK 

    • Serum persistence of intact antibodies is governed by interaction between Fc and FcRn receptor 

    • Point mutations can weaken or eliminate FcRn interactions and accelerate clearance 

    • CEA-specific scFv-Fc fragments: 

    - Wild-type 

    - Single mutant: H435Q, I253A, H310A 

    - Double mutant (DM) H435Q/H310A 

    • Serum half-lives from 8 – 80 h 

  • Patent

    WO2021236645A1

  • Publication

  • Attachment

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