Institutional Repository

The UDSpace Institutional Repository collects and disseminates research material from the University of Delaware.

  • Faculty, staff, and graduate students can deposit their research material directly into UDSpace. Faculty may use UDSpace to fulfill the University of Delaware Faculty Senate Open Access Resolution, and in many cases may use it to fulfill open access requirements from grant funding agencies.
  • Departments can use UDSpace to publish or distribute their working papers, technical reports, or other research material.
  • UDSpace also includes all doctoral dissertations from winter 2014 forward, and all master's theses from fall 2009 forward.

To learn more about UDSpace, and how you can make your research openly accessible to the public, visit our UDSpace Policies website.

 

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Recent Submissions

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2025, 28th Issue, part 2
(Newark, Del.: Chesapeake Pub. Corp., 2025-07-11) Newark post
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2025, 28th Issue, part 1
(Newark, Del.: Chesapeake Pub. Corp., 2025-07-11) Newark post
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2025, 27th Issue, part 2
(Newark, Del.: Chesapeake Pub. Corp., 2025-07-04) Newark post
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2025, 27th Issue, part 1
(Newark, Del.: Chesapeake Pub. Corp., 2025-07-04) Newark post
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TARGETING MESOTHELIN IN PEDIATRIC ACUTE MYELOID LEUKEMIA WITH DUAL ANTIBODY-COATED POLY(LACTIC-CO-GLYCOLIC ACID) NANOPARTICLES
(University of Delaware, 2025-05) Avery Wolverton
Acute myeloid leukemia (AML) is a rare but aggressive cancer, accounting for approximately seven new cases per 1 million children annually. It arises from the malignant transformation of hematopoietic stem and progenitor cells, leading to an accumulation of immature, nonfunctional myeloblasts in the bone marrow. Standard treatments, such as chemotherapy and stem cell transplantation, have high relapse rates and significant toxicity, emphasizing the need for more effective therapies. Immunotherapy has emerged as a promising treatment strategy, however, specific targeting of AML cells and maintaining extended circulation times of administered agents remain major challenges. Mesothelin (MSLN) has been identified as an attractive immunotherapeutic target that is overexpressed in one-third of young adult and pediatric AML patients with limited expression in normal bone marrow. Here, we report the design, characterization, and validation of dual antibody coated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (duNPs) that recruit T lymphocytes to AML to induce specific cytotoxicity of AML cells. PLGA NPs were coated with anti-MSLN (Amatuximab) and anti-CD3 antibodies (OKT3) and characterized for size, charge, and concentration. Microscopy analysis revealed duNPs pull T lymphocytes and MSLN-expressing NOMO-1 cells into clusters to induce cytotoxicity. Additionally, the duNPs facilitated significantly higher T cell activation compared to bare NPs, as confirmed by elevated CD69 levels, suggesting the duNPs successfully engage T cells. To evaluate the efficacy of duNPs in promoting T cell induced killing of AML cells, the T cells were incubated with AML cells and treated with increasing amounts of bare NPs or duNPs for 16 hours before assessing cell viability. duNP treatment selectively killed AML cells in a dose-dependent manner compared to bare NPs. Collectively, our data suggest that dual antibody-coated NPs are effective agents to recruit T lymphocytes to MSLN-expressing AML cells, increase T cell activation, and induce AML cell death.