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FLT3/CD99 Bispecific Antibody-Based Nanoparticles for Acute Myeloid Leukemia.
Ali, Atham; Phan, Alvin; Vaikari, Vijaya; Park, Mincheol; Pospiech, Mateusz; Chu, Ryan; Meng, Yiting; MacKay, John A; Alachkar, Houda.
Afiliación
  • Ali A; Department of Clinical Pharmacy, USC School of Pharmacy, University of Southern California, Los Angeles, California.
  • Phan A; Department of Pharmacology and Pharmaceutical Sciences, USC School of Pharmacy, University of Southern California, Los Angeles, California.
  • Vaikari V; Department of Clinical Pharmacy, USC School of Pharmacy, University of Southern California, Los Angeles, California.
  • Park M; Department of Pharmacology and Pharmaceutical Sciences, USC School of Pharmacy, University of Southern California, Los Angeles, California.
  • Pospiech M; Department of Clinical Pharmacy, USC School of Pharmacy, University of Southern California, Los Angeles, California.
  • Chu R; Department of Clinical Pharmacy, USC School of Pharmacy, University of Southern California, Los Angeles, California.
  • Meng Y; Department of Clinical Pharmacy, USC School of Pharmacy, University of Southern California, Los Angeles, California.
  • MacKay JA; Department of Pharmacology and Pharmaceutical Sciences, USC School of Pharmacy, University of Southern California, Los Angeles, California.
  • Alachkar H; Department of Ophthalmology, USC Roski Eye Institute, USC Keck School of Medicine, University of Southern California, Los Angeles, California.
Cancer Res Commun ; 4(8): 1946-1962, 2024 Aug 01.
Article en En | MEDLINE | ID: mdl-39007347
ABSTRACT
Cluster of differentiation 99 (CD99) is a receptor that is significantly upregulated in acute myeloid leukemia (AML). FMS-like tyrosine kinase 3 internal tandem duplication mutation in AML (FLT3-ITD AML) exhibits even higher levels of CD99 expression. Our group previously employed a novel peptide platform technology called elastin-like polypeptides and fused it with single-chain antibodies capable of binding to FLT3 (FLT3-A192) or CD99 (CD99-A192). Targeting either FLT3 or CD99 using FLT3-A192 or CD99-A192 led to AML cell death and reduced leukemia burden in AML mouse models. Here, we report on the development of a novel Co-Assembled construct that is capable of binding to both CD99 and FLT3 and the antileukemia activity of the bispecific construct in FLT3-ITD AML preclinical models. This dual-targeting Co-Assembled formulation exhibits cytotoxic effects on AML cells (AML cell lines and primary blasts) and reduced leukemia burden and prolonged survival in FLT3-ITD AML mouse models. Altogether, this study demonstrates the potential of an innovative therapeutic strategy that targets both FLT3 and CD99 in FLT3-ITD AML.

SIGNIFICANCE:

This study investigates a dual-targeting strategy in acute myeloid leukemia (AML), focusing on FLT3 and CD99. The approach demonstrates enhanced therapeutic potential, presenting a novel option for AML treatment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Mieloide Aguda / Anticuerpos Biespecíficos / Tirosina Quinasa 3 Similar a fms / Nanopartículas / Antígeno 12E7 Límite: Animals / Female / Humans Idioma: En Revista: Cancer Res Commun Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Mieloide Aguda / Anticuerpos Biespecíficos / Tirosina Quinasa 3 Similar a fms / Nanopartículas / Antígeno 12E7 Límite: Animals / Female / Humans Idioma: En Revista: Cancer Res Commun Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos