Studies examining the efficacy of therapeutically enhanced human mast cells as a cancer immunotherapy

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)

Mohammad Fereydouni (Creator)

Institution

The University of North Carolina at Greensboro (UNCG )

Web Site: http://library.uncg.edu/

Advisor

Christopher Kepley

Abstract: The emergence of cancer immunotherapies utilizing adoptive cell transfer (ACT) continues to be one of the most promising strategies for cancer treatment. Mast cells (MCs), ubiquitous tissue cells most commonly associated with Type I hypersensitivity, bind immunoglobin E (IgE) with high affinity, produce anti-cancer agents such as tumor necrosis factor alpha (TNF-?) and granulocyte macrophage colony-stimulating factor (GM-CSF), and populate practically all tumor microenvironments. Yet, the role of MCs in cancer pathologies remains controversial as direct evidence for anti-tumor or pro-tumor effects are lacking. Here we initially present an improved method for obtaining a large number of human MCs from adipose tissue. The proposed method has several advantages over current methods and can serve as a new source of human MCs for more realistic studies on the biology of this cell type in humans. Then, we found that HER2/neu tumor-specific IgE-sensitized MCs bound, penetrated, and killed HER2/neu-positive tumor masses in vitro. Further in solid tumor human breast cancer (BC) xenograft mouse models, infusion of HER2/neu IgE-sensitized human adipose-derived mast cells (ADMC) co-localized to BC cells, decreased tumor burden, and prolonged overall survival without signs of toxicity. These studies suggest MCs can be polarized from Type I hypersensitivity-mediating cells to tumor-attacking cells and may provide further options for cancer therapeutics for which tumor targeted IgEs are available. [This abstract may have been edited to remove characters that will not display in this system. Please see the PDF for the full abstract.]

Studies examining the efficacy of therapeutically enhanced human mast cells as a cancer immunotherapy
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Created on 12/1/2021
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Additional Information

Publication

Dissertation

Language: English

Date: 2021

Keywords

AllergoOncology, Cancer Immunotherapy, IgE antibody, Mast cells, Tumor eradication

Subjects

Cancer $x Immunotherapy

Tumors $x Immunological aspects

Mast cells $x Immunology

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