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

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

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 treatme...

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Main Authors: Nuchjira Takheaw, Thanathat Pamonsupornwichit, Ratthakorn Chaiwut, Kamonporn Kotemul, Kanokporn Sornsuwan, On-anong Juntit, Umpa Yasamut, Passaworn Cheyasawan, Witida Laopajon, Watchara Kasinrerk, Chatchai Tayapiwatana
Format: Article
Language:English
Published: MDPI AG 2024-11-01
Series:Biomolecules
Subjects:
CD99
T cell malignancies
antibody humanization
antibody therapy
apoptosis
Online Access:https://www.mdpi.com/2218-273X/14/11/1422
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Summary: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<sup>−10</sup> 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.
ISSN:2218-273X

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