Engineering of therapeutic antibodies to minimize immunogenicity and optimize function

Area of Science:

• Biotechnology
• Immunology
• Pharmacology

Background:

• The development of monoclonal antibody therapeutics was hindered by the human anti-mouse antibody (HAMA) response, which limits the efficacy of murine-derived antibodies.
• Early therapeutic antibody development relied on murine antibodies, leading to significant immunogenic reactions in patients.

Purpose of the Study:

• To review the evolution of strategies aimed at overcoming the immunogenicity of therapeutic antibodies.
• To discuss advancements in engineering antibody properties beyond reduced immunogenicity, focusing on antigen-binding and effector functions.

Main Methods:

• Review of scientific literature and technological advancements in antibody engineering.
• Analysis of strategies including antibody chimerization, humanization, de-immunization, and the development of human-sequence antibodies.
• Examination of techniques for optimizing antibody antigen-binding domains and effector functions.

Main Results:

• Successful development of various antibody engineering techniques (chimeric, humanized, de-immunized, human-sequence) to mitigate the HAMA response.
• Established methods for enhancing antibody antigen-binding affinity, stability, and effector functions like antibody-dependent cellular cytotoxicity and complement-dependent cellular cytotoxicity.

Conclusions:

• Significant progress has been made in reducing the immunogenicity of therapeutic antibodies, enabling their broader clinical application.
• Ongoing research focuses on fine-tuning antibody characteristics to maximize therapeutic potential and clinical outcomes.