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Enhanced T cell activation and cytotoxicity against AML via targeted anti-CD99 nanoparticle treatment.

Authors :
Kadam S
Ali A
Pospiech M
Onyemaechi S
Meng Y
Dhuri K
MacKay JA
Alachkar H
Source :
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2024 Aug 20; Vol. 179, pp. 117265. Date of Electronic Publication: 2024 Aug 20.
Publication Year :
2024
Publisher :
Ahead of Print

Abstract

CD99 is a transmembrane protein overexpressed in Acute Myeloid Leukemia (AML), presenting a potential novel therapeutic target. Our group has previously developed anti-CD99-A192 (α-CD99-A192), comprising of single chain variable fragment (scFv) and elastin-like polypeptides (ELPs), and reported promising anti-leukemic activity in AML preclinical models. Treatment with α-CD99-A192 induced apoptosis in AML cell lines and prolonged survival in AML xenograft models. Considering CD99's expression and role in T cell activation, in the current study, we propose that α-CD99-A192 plays a dual function, i.e., targeting leukemic cells and activating T cells. This manuscript reports the effects of α-CD99-A192 on T cells in the context of AML. α-CD99-A192 treatment enhances T cell proliferation and activation and increases the release of pro-inflammatory cytokines along with increased aggregation of T cells, which culminates in heightened cytotoxicity against leukemic cells. Altogether, these findings suggest α-CD99-A192 enhances T cell activation and cytotoxic potential consistent with dual mechanisms of action for α-CD99-A192.<br />Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Details

Language :
English
ISSN :
1950-6007
Volume :
179
Database :
MEDLINE
Journal :
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
Publication Type :
Academic Journal
Accession number :
39167846
Full Text :
https://doi.org/10.1016/j.biopha.2024.117265