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Exploring the Biological Activity of a Humanized Anti-CD99 ScFv and Antibody for Targeting T Cell Malignancies.

Authors :
Takheaw, Nuchjira
Pamonsupornwichit, Thanathat
Chaiwut, Ratthakorn
Kotemul, Kamonporn
Sornsuwan, Kanokporn
Juntit, On-anong
Yasamut, Umpa
Cheyasawan, Passaworn
Laopajon, Witida
Kasinrerk, Watchara
Tayapiwatana, Chatchai
Source :
Biomolecules (2218-273X); Nov2024, Vol. 14 Issue 11, p1422, 19p
Publication Year :
2024

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<superscript>−10</superscript> 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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
2218273X
Volume :
14
Issue :
11
Database :
Complementary Index
Journal :
Biomolecules (2218-273X)
Publication Type :
Academic Journal
Accession number :
181165278
Full Text :
https://doi.org/10.3390/biom14111422