Exploring the Biological Activity of a Humanized Anti-CD99 ScFv and Antibody for Targeting T Cell Malignancies
3
Issued Date
2024-11-01
Resource Type
eISSN
2218273X
Scopus ID
2-s2.0-85210447932
Journal Title
Biomolecules
Volume
14
Issue
11
Rights Holder(s)
SCOPUS
Bibliographic Citation
Biomolecules Vol.14 No.11 (2024)
Suggested Citation
Takheaw N., Pamonsupornwichit T., Chaiwut R., Kotemul K., Sornsuwan K., Juntit O.A., Yasamut U., Cheyasawan P., Laopajon W., Kasinrerk W., Tayapiwatana C. Exploring the Biological Activity of a Humanized Anti-CD99 ScFv and Antibody for Targeting T Cell Malignancies. Biomolecules Vol.14 No.11 (2024). doi:10.3390/biom14111422 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/102305
Title
Exploring the Biological Activity of a Humanized Anti-CD99 ScFv and Antibody for Targeting T Cell Malignancies
Author's Affiliation
Corresponding Author(s)
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Abstract
CD99, a type I transmembrane protein, emerges as a promising therapeutic target due to its heightened expression in T cell acute lymphoblastic leukemia (T-ALL). This characteristic renders it a potential marker for minimal residual disease detection and an appealing target for antibody-based treatments. Previous studies have revealed that a mouse monoclonal antibody, mAb MT99/3, selectively binds to CD99, triggering apoptosis in T-ALL/T-LBL cells while preserving the integrity of healthy cells. By targeting CD99, mAb MT99/3 suppresses antigen presentation and disrupts T cell functions, offering promise for addressing hyperresponsive T cell conditions. To facilitate clinical translation, we developed a humanized ScFv variant of mAb MT99/3, termed HuScFvMT99/3 in “ScFvkh” design. Structural analysis confirms its resemblance to the original antibody, and the immunoreactivity of HuScFvMT99/3 against CD99 is preserved. The fully humanized version of antibody HuMT99/3 was further engineered, exhibiting similar binding affinity at the 10−10 M level and specificity to the CD99 epitope without antigenic shift. HuMT99/3 demonstrates remarkable selectivity, recognizing both malignant and normal T cells but inducing apoptosis only in T-ALL/T-LBL cells, highlighting its potential for safe and targeted therapy.