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Dissertation
Immunomodulation by non-thermal plasma: toward immunotherapies for HIV-1 infection and leukemia
Doctor of Philosophy (Ph.D.), Drexel University
Jul 2021
DOI:
https://doi.org/10.17918/00000833
Abstract
Immunological control of disseminated viral infections and cancers of the hematopoietic system can be achieved through robust CD8+ T cell responses. However, immune dysfunctions in patients with these conditions can lead to control failures and disease chronicity. As the first steps toward developing a novel immunological therapy, we investigated non-thermal plasma (NTP), which is a partially ionized gas containing reactive oxygen and nitrogen species (RONS). NTP application to cells induces oxidative stress and stimulates emission of immunogenic damage-associated molecular patterns (DAMPs) known to promote various functions of antigen presenting cells (APCs). These NTP-mediated effects and the resulting augmentation of immune responses were observed in several in vivo cancer models. However, the therapeutic effects of NTP against hematologic viral infections and hematopoietic cancers have not yet been studied. We investigated the immunomodulatory potential of NTP in the context of two challenging hematologic conditions: HIV-1 infection and acute T lymphoblastic leukemia. We hypothesized that NTP can be used to enhance the immunogenicity of the HIV-1-infected T cells or malignant T cells to offset multiple dysfunctions in the immune response in both of these diseases. Application of NTP to the J-Lat CD4+ T lymphocyte cell line, a model for latent HIV-1 infection, resulted in emission of pro-phagocytic and pro-chemotactic DAMPs in addition to modulation of molecules associated with antigen presentation. Accordingly, NTP-exposed J-Lat cells stimulated monocyte migration and maturation, as well as phagocytosis of NTP-exposed J-Lat cells. Similar immunostimulatory effects were observed after applying NTP to the leukemic Jurkat CD4+ T cell line and leukemic THP-1 monocytes, suggesting NTP-mediated immunomodulation as a therapeutic approach for leukemias may also be feasible. These results provide insights for a novel type of treatment in which patient cells are exposed ex vivo to NTP and then injected into the patient as a personalized immunotherapy. These studies provide the foundation for the development of NTP-based immunotherapies designed to boost CD8+ T cell responses that will offer drug-free control of HIV-1 infection, as well as immunological control of hematologic malignancies such as leukemia.
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Details
- Title
- Immunomodulation by non-thermal plasma
- Creators
- Hager Mohamed
- Contributors
- Fred C. Krebs (Advisor)Vandana Miller (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xxv, 372 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Microbiology and Immunology; College of Medicine; Drexel University
- Other Identifier
- 991015274071004721