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Engineered PSCA antibody for Targeted Radiotherapy

City of Hope

Antibody

Oncology

Hit To Lead or Lead Optimization

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 

WO2021236645A1

City of Hope_Overview_Engineered PSCA antibody for Targeted Radiotherapy.pdf
City of Hope_Patent_WO2021236645A1.pdf
City of Hope_Slide deck_Engineered PSCA antibody for Targeted Radiotherapy.pdf