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Humanized antibodies for antiviral therapy
M S Co1, M Deschamps, R J Whitley
1Protein Design Labs, Inc., Mountain View, CA 94043.
Summary
Humanized antibodies, created using computer modeling, retain the therapeutic properties of mouse antibodies. This advancement offers potential for effective treatments against viral infections like herpes simplex virus.
Area of Science:
- Immunology
- Biotechnology
- Virology
Background:
- Antibody therapy shows promise for treating cancer, autoimmune disorders, and viral infections.
- Murine monoclonal antibodies are immunogenic in humans, limiting their therapeutic use.
- Production of human monoclonal antibodies remains challenging.
Purpose of the Study:
- To humanize murine monoclonal antibodies against herpes simplex virus (HSV) glycoproteins gB and gD.
- To assess if humanized antibodies retain binding activity and biological properties of the original murine antibodies.
Main Methods:
- Utilized computer modeling to introduce the hypervariable regions of murine antibodies into human framework sequences.
- Combined these with human constant regions to create humanized antibodies.
- Evaluated binding affinity, virus neutralization capacity, and cell protection.
Main Results:
- Successfully generated humanized monoclonal antibodies against HSV gB and gD.
- Humanized antibodies demonstrated retained binding activities compared to murine counterparts.
- Virus neutralization and cell protection assays confirmed the preservation of biological functions.
Conclusions:
- Computer-aided humanization effectively preserves the therapeutic potential of murine monoclonal antibodies.
- Humanized antibodies against HSV gB and gD are viable candidates for further therapeutic development.
- This approach overcomes the immunogenicity issues associated with murine antibodies for human treatment.