The First Bagshawe lecture. Towards generating cytotoxic agents at cancer sites

Area of Science:

• Oncology
• Pharmacology
• Biotechnology

Background:

• Targeted anti-cancer agent delivery faces limitations including molecular heterogeneity, macromolecule pharmacokinetics, and host immune responses.
• Current strategies struggle with effective drug distribution within heterogeneous tumor cell populations.

Purpose of the Study:

• To investigate a novel strategy for targeted cancer therapy using enzyme-prodrug systems.
• To address limitations in current anti-cancer agent delivery and efficacy.

Main Methods:

• Utilizing antibodies or vectors to deliver enzymes lacking human homologues to tumor sites.
• Administering a non-toxic prodrug that is converted to a toxic agent by the tumor-localized enzyme.
• Employing techniques to clear residual enzyme activity from circulation.
• Exploring genetic engineering for human immunoglobulins with tumor-binding and catalytic properties.

Main Results:

• The proposed enzyme-prodrug system generates a potent cytotoxic molecule at the tumor site.
• The generated toxin can penetrate tumor masses and cross cell membranes effectively.
• Genetic engineering offers potential for reduced host antibody response through humanized antibodies.

Conclusions:

• This enzyme-prodrug approach shows promise for overcoming key obstacles in targeted cancer therapy.
• Further development of antibody specificity and enzyme-prodrug systems is crucial for clinical success.
• Early findings suggest significant progress can be made in this therapeutic direction.