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#prodrug

2 public questions tagged with this topic.

Immunological Applications

The prodrug in abzyme therapy is:

Abzyme-directed prodrug therapy also known as ADAPT aims to combine tumor-targeting specificity of antibodies with catalytic turnover allowing one antibody molecule to activate many prodrug molecules amplifying effect. Conventional systemic chemotherapy distributes throughout body causing dose limiting myelosuppression, alopecia, mucositis due to toxicity to rapidly dividing normal tissues such as bone marrow and gastrointestinal epithelium. Prodrug strategy masks cytotoxic warhead with cleavable moiety ester, carbamate, glucuronide, or phosphate rendering molecule 100 to 1000 fold less toxic,

Ref: Shabat et al PNAS 1995 ADAPT abzyme prodrug site activation; US Patent 5948647 antibody directed prodrug therapy.

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Immunological Applications

The prodrug in abzyme therapy is:

Abzyme-directed enzyme prodrug therapy ADEPT-like strategy employs two-step approach achieving localized drug activation minimizing systemic exposure toxicity. First step abzyme engineered single-chain variable fragment fused tumor-targeting antibody anti-CEA or anti-HER2 or PEGylated enhancing permeability retention leaky tumor vasculature poor lymphatic drainage accumulates tumor interstitium reaching micromolar concentration while blood levels decline rapidly clearance liver kidney. Abzyme remains enzymatically active non-toxic alone because mammalian substrates lacking scissile bond recogn

Ref: Bagshawe ADEPT Abzyme Prodrug Activation Review 1994; PMC Abzyme Prodrug Therapy Targeted Release Mechanism 2020; Nature Biotech Abzyme Directed Therapy Concept Paper.

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