Antibody constructs in cancer therapy: protein engineering strategies to improve exposure in solid tumors

Area of Science:

• Oncology
• Immunology
• Biotechnology

Background:

• Solid tumors constitute over 85% of human cancers, yet only 25% of approved monoclonal antibody (mAb) cancer therapies target them.
• Limited exposure of mAbs within solid tumors is a significant challenge hindering therapeutic efficacy.

Purpose of the Study:

• To provide a conceptual framework for optimizing antibody constructs for solid tumor therapy.
• To highlight the importance of physical properties in determining antibody tumor exposure and retention.

Main Methods:

• Reviewing advancements in tumor biology, protein engineering, and macromolecular transport modeling.
• Analyzing various antibody constructs, including fragments, single-chain variable fragments (scFvs), and engineered dimers.
• Focusing on manipulating molecular size, charge, valence, and binding affinity.

Main Results:

• Demonstrated that physical properties critically influence antibody penetration and retention in tumors.
• Showcased how different antibody formats (e.g., diabodies, minibodies) can be engineered to optimize these properties.
• Identified molecular size, charge, valence, and binding affinity as key manipulable factors.

Conclusions:

• Optimizing antibody physical properties is essential for enhancing tumor exposure and efficacy.
• Engineered antibody constructs offer promising strategies for overcoming solid tumor barriers.
• These advancements pave the way for more successful antibody-based therapies for solid tumors.