Humanized anti-CD11d monoclonal antibodies suitable for basic research and therapeutic applications

Antibody Therapeutics, 2025 · DOI: 10.1093/abt/tbae031 · Published: December 16, 2024

Simple Explanation

The study focuses on developing humanized antibodies against CD11d, a protein involved in inflammation, for potential treatment of conditions like neurotrauma and sepsis. Researchers created several versions of these antibodies and tested their ability to bind to immune cells and reduce inflammation in a rat model of spinal cord injury. One antibody, anti-CD11d-2, was found to bind effectively without causing unwanted inflammatory signaling, making it a promising candidate for further therapeutic development.

Study Duration

Not specified

Participants

Primary human leukocytes, THP-1 monocytic cell line, Wistar rats

Evidence Level

Not specified

Key Findings

1
The researchers successfully developed and characterized five humanized anti-CD11d monoclonal antibodies.
2
The humanized antibodies, particularly anti-CD11d-3, demonstrated therapeutic efficacy in a rat model of spinal cord injury by reducing neutrophil infiltration and improving locomotor recovery.
3
The anti-CD11d-2 clone exhibited high binding affinity to CD11d, bound both active and inactive conformations, and did not induce pro-inflammatory signaling in vitro.

Research Summary

This research describes the creation and characterization of humanized anti-CD11d monoclonal antibodies as potential therapeutics for inflammatory conditions. In vitro and in vivo studies demonstrated that these antibodies, particularly anti-CD11d-2 and anti-CD11d-3, retained the therapeutic benefits of the original murine antibodies, improving outcomes in a rat spinal cord injury model. The study also revealed new insights into CD11d expression and regulation, including the impact of CK2 inhibition on β2 integrin expression and the mismatch between total and surface-level CD11d expression.

Practical Implications

Therapeutic Development

The humanized anti-CD11d antibodies provide a foundation for developing targeted immunotherapies for neurotrauma, sepsis, and atherosclerosis.

Research Tool

The anti-CD11d-2 clone can be used as a refined detection tool for studying CD11d/CD18 expression and function.

Understanding CD11d Regulation

The findings on CK2 inhibition and CD11d expression contribute to a deeper understanding of the post-transcriptional regulation of CD11d and β2 integrins.

Study Limitations

1
The study primarily used a rat model for in vivo validation, and further studies are needed to confirm the efficacy and safety of these antibodies in human clinical trials.
2
The mechanistic pathway for CD11d/CD18 signaling cascade has not been fully elucidated.
3
Further studies are needed to determine the cause of the discrepancy between total and surface-level CD11d expression.

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