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Visualization And Characterization Of The Immunological Synapse Between Chlorotoxin Chimeric Antigen (Cltx-Car) Redirected T Cells And Targeted Glioblastoma Tumors, Arianna Livi 2023 Claremont Colleges

Visualization And Characterization Of The Immunological Synapse Between Chlorotoxin Chimeric Antigen (Cltx-Car) Redirected T Cells And Targeted Glioblastoma Tumors, Arianna Livi

CMC Senior Theses

Chimeric Antigen Receptor T (CAR-T) cells have demonstrated anti-tumor activity against aggressive and invasive cancers such as glioblastoma (GBM); however, clinical response rates remain low in clinical trial studies. Tumor heterogeneity and tumor microenvironment conditions pose significant challenges for treatment of GBM, thus continuous optimization of CAR-T cell therapies and identification of novel, widely expressed, and highly specific GBM antigens are vital to better patient outcomes. A newly developed CAR-T cell construct incorporating chlorotoxin (CLTX) as the targeting domain exhibited broad GBM-targeting capabilities and elicited potent cytotoxic effects during preclinical studies and is currently being tested in a phase I …


Investigating The Pi3k/Akt/Atm Pathway, Telomeric Dna Damage, T Cell Death, And Crispr/Cas9-Mediated Gene Editing During Acute And Chronic Hiv Infection, Sushant Khanal 2022 East Tennessee State University

Investigating The Pi3k/Akt/Atm Pathway, Telomeric Dna Damage, T Cell Death, And Crispr/Cas9-Mediated Gene Editing During Acute And Chronic Hiv Infection, Sushant Khanal

Electronic Theses and Dissertations

Human Immunodeficiency Virus (HIV) infection initiates major metabolic and cell- survival complications. Anti-retroviral therapy (ART) is the current approach to suppress active HIV replication to a level of undetected viral load, but it is not a curative approach. Newer and sophisticated gene editing technologies could indeed be a potent antiviral therapy to achieve a clinical sterilization/cure of HIV infection. Chronic HIV patients, even under a successful ART regimen, exhibit a low-grade inflammation, immune senescence, premature aging, telomeric DNA attrition, T cell apoptosis, and cellular homeostasis. In this dissertation, we investigated CD4 T cell homeostasis, degree of T cell apoptosis, an …


A Novel Transmembrane Ligand Inhibits T Cell Receptor Activation, Yujie Ye 2022 University of Tennessee, Knoxville

A Novel Transmembrane Ligand Inhibits T Cell Receptor Activation, Yujie Ye

Doctoral Dissertations

T lymphocytes (T cells) play essential roles in the adaptive immune system. Each mature T cell expresses one type of functional T cell receptor (TCR). The TCR recognizes antigens bound to the major histocompatibility complex (MHC) in antigen presenting cells. The resulting stimulation signal crosses the transmembrane domain of TCR and initiates downstream signaling cascades. The human immune system relies on TCRs to recognize a variety of pathogens. Normally, TCR can distinguish the self-antigens from pathogenic antigens. However, dysfunction or aberrant expression of TCRs causes different inflammatory and autoimmune diseases, which afflict millions of people annually (Chapter I). Current treatments …


Using The Embl-Ebi Clustal Omega Tool To Calculate Diversity Of Heavy Chain Phage-Display Libraries, Michael Bodri, Shane A. Webb 2022 University of North Georgia

Using The Embl-Ebi Clustal Omega Tool To Calculate Diversity Of Heavy Chain Phage-Display Libraries, Michael Bodri, Shane A. Webb

Georgia Journal of Science

Here we show that traditional Sanger sequencing combined with analysis tools available from the European Molecular Biology Laboratory-European Bioinformatics Institute (EMBL-EBI), specifically EMBOSS Transeq and Clustal Omega, is extremely effective in the analysis of naïve phage display antibody libraries for the determination of library size and diversity. The free tools are easy to use and require little manipulation of reads by hand, allowing analysis to be performed on a standard personal computer. Utilization of this technique has applicability to researchers with limited access to deep sequencing. The primary drawback to this analysis methodology is that antibodies with particular molecular or …


The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, Carolina Garcia Garcia 2022 The Texas Medical Center Library

The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, Carolina Garcia Garcia

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with dismal prognosis. The only curative option for patients is surgery, but over 80% of patients are not surgical candidates. Unfortunately, PDAC is resistant to the three remaining options. PDAC is characterized by a profoundly hypoxic and immunosuppressive stroma, which contributes to its therapeutic recalcitrance. Alpha-smooth muscle actin+ (αSMA+) cancer-associated fibroblasts (CAFs) are the most abundant stromal component, as well as mediators of stromal deposition. The hypoxia-inducible factors (HIF1 and HIF2) coordinate responses to hypoxia, yet, despite their known association to poor patient outcomes, their functions within the PDAC tumor microenvironment (TME) …


Immunotherapeutic Effects Of Intratumorally Injected Zymosan-Adenovirus Conjugates Encoding Constant Active Irfs In A Melanoma Mouse Model, Margaret Musick 2022 Clemson University

Immunotherapeutic Effects Of Intratumorally Injected Zymosan-Adenovirus Conjugates Encoding Constant Active Irfs In A Melanoma Mouse Model, Margaret Musick

All Dissertations

Current immunotherapies are only effective in a fraction of cancer patients. One of the main contributing factors to therapy resistance and overall poor prognosis is the immune status of the tumor microenvironment (TME). Tumor-associated macrophages (TAMs) have been shown to have significant influence on the immune status of the TME. As key players in maintaining tissue homeostasis, macrophages exhibit a broad range of phenotypes and functions, making TAMs a promising target for immunomodulatory therapies. As liaisons between innate and adaptive immunity, TAMs can promote a robust anti-tumor response involving both innate and adaptive immunity. This study investigated the potential of …


Macrophage Rac2 Promotes Suppression Of Germination During Aspergillus Fumigatus Infection, Chris D. Tanner 2022 Clemson University

Macrophage Rac2 Promotes Suppression Of Germination During Aspergillus Fumigatus Infection, Chris D. Tanner

All Theses

Aspergillus fumigatus is a fungus found ubiquitously in the environment including in the air we breathe. Though not a threat to most people, immunodeficient or immunosuppressed individuals are at risk for developing severe infection, including the life-threatening condition of invasive aspergillosis. The hematopoietic cell specific GTPase protein Rac2 is associated with major roles in innate immune defense. Currently Rac2 has been demonstrated to be crucial for survival against a variety of infections. Here, we use a rac2 null mutant zebrafish line and morpholino approaches to elucidate roles of Rac2 in mounting the macrophage host defense response against A. fumigatus infection. …


The Herpes Simplex Virus Type-1 (Hsv-1), Vc2 Live-Attenuated Vaccine Strain Induces Robust Antitumor Immune Responses And Ameliorates Intra-Tumor Immunosuppression In An Immunocompetent B16f10-Derived Murine Melanoma Model, Ifeanyi Kingsley Uche 2022 Louisiana State University and Agricultural and Mechanical College

The Herpes Simplex Virus Type-1 (Hsv-1), Vc2 Live-Attenuated Vaccine Strain Induces Robust Antitumor Immune Responses And Ameliorates Intra-Tumor Immunosuppression In An Immunocompetent B16f10-Derived Murine Melanoma Model, Ifeanyi Kingsley Uche

LSU Doctoral Dissertations

Current cancer immunotherapies include immune checkpoint inhibitors, adoptive cellular therapy, and cancer vaccines. While some of these therapies have met with great clinical success, they are associated with several limitations. Oncolytic virotherapy (OVT) has emerged as a bonafide promising immunotherapy, that uses viral infection to liberate tumor antigens in an immunogenic context to promote the development of anti-tumor immune responses. At present, Talimogene laherparepvec (T-VEC; Imlygic™), a modified type 1 herpes simplex virus (HSV-1) is the only FDA approved OVT for human cancer treatment (melanoma). While T-VEC is associated with limited response rates, its modest efficacy supports the continued development …


Conventional Therapies Deplete Brain-Infiltrating Adaptive Immune Cells In A Mouse Model Of Group 3 Medulloblastoma Implicating Myeloid Cells As Favorable Immunotherapy Targets, Zahra Abbas, Courtney George, Mathew Ancliffe, Meegan Howlett, Anya C. Jones, Mani Kuchibhotla, Robert J. Wechsler-Reya, Nicholas G. Gottardo, Raelene Endersby 2022 Edith Cowan University

Conventional Therapies Deplete Brain-Infiltrating Adaptive Immune Cells In A Mouse Model Of Group 3 Medulloblastoma Implicating Myeloid Cells As Favorable Immunotherapy Targets, Zahra Abbas, Courtney George, Mathew Ancliffe, Meegan Howlett, Anya C. Jones, Mani Kuchibhotla, Robert J. Wechsler-Reya, Nicholas G. Gottardo, Raelene Endersby

Research outputs 2022 to 2026

Medulloblastoma is the most common childhood brain cancer. Mainstay treatments of radiation and chemotherapy have not changed in decades and new treatment approaches are crucial for the improvement of clinical outcomes. To date, immunotherapies for medulloblastoma have been unsuccessful, and studies investigating the immune microenvironment of the disease and the impact of current therapies are limited. Preclinical models that recapitulate both the disease and immune environment are essential for understanding immune-tumor interactions and to aid the identification of new and effective immunotherapies. Using an immune-competent mouse model of aggressive Myc-driven medulloblastoma, we characterized the brain immune microenvironment and changes induced …


Determining Effective Treatment Regimens For Breast Cancer Using Combined Immunotherapy And Chemotherapy In Vivo, Akhila R. Kunuthuru, Laura Graham, Harry D. Bear MD, PhD 2022 Virginia Commonwealth University

Determining Effective Treatment Regimens For Breast Cancer Using Combined Immunotherapy And Chemotherapy In Vivo, Akhila R. Kunuthuru, Laura Graham, Harry D. Bear Md, Phd

Undergraduate Research Posters

Breast cancer has the highest incidence rate of all cancers globally in women, and those of African descent, especially West African females, face higher rates of triple-negative breast cancer (TNBC), a more aggressive form of breast cancer. Immunotherapy for breast cancer is a relatively new treatment option, and research is ongoing to identify the best combination treatments for increasing survival of those diagnosed with TNBC. Eganelisib (IPI-549: a PI3K-gamma inhibitor that works to shift M2 macrophages to M1 to augment T cell function) with other combinatory treatments has shown promising results in reducing tumor growth and increasing survival in mice. …


Response And Molecular Control Of Cd8 T Cells During Infection And Cancer, Nicholas K. Preiss Dr. 2022 Dartmouth College

Response And Molecular Control Of Cd8 T Cells During Infection And Cancer, Nicholas K. Preiss Dr.

Dartmouth College Ph.D Dissertations

CD8 T cells are potent immune effector cells capable of vast clonal expansion and clearance of infected or cancerous cells. After control of the pathogenic insult, CD8 T cells develop into quiescent, long-lived memory populations that are poised to mediate rapid protection upon reencounter with cognate antigen. These properties make control of CD8 T cell responses a highly desirable outcome of vaccine strategies and immunotherapy. Therefore, understanding how the effector function and memory differentiation of CD8 T cells are controlled at a molecular level is of great importance. In the context of infection with gammaherpesviruses (γHV), which form a latent …


Methods For Characterization Of Cl-001 Derived Exosomes As A Stimulating Agent For Nk Cells For Immunotherapy, Ilana Gomez Diaz 2022 University of Central Florida

Methods For Characterization Of Cl-001 Derived Exosomes As A Stimulating Agent For Nk Cells For Immunotherapy, Ilana Gomez Diaz

Honors Undergraduate Theses

The immune system is a complex set of cells in the body that work to prevent disease or infection by recognizing and eliminating foreign material or unhealthy cells. One essential type of immune cell that is part of the innate immune response are Natural Killer (NK) cells. These cytotoxic effector lymphocytes can detect certain unhealthy cells, such as cancer cells, that normal B and T cells would miss. For example, many tumor cells have evolved to bypass immune system surveillance by not expressing major histocompatibility complex class I molecules (MHC class I), on their surface, reducing recognition by cytotoxic T …


Stat3 Inhibits Type I Interferon Signaling In Type I Conventional Dendritic Cells, Taylor Chrisikos 2021 The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

Stat3 Inhibits Type I Interferon Signaling In Type I Conventional Dendritic Cells, Taylor Chrisikos

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Conventional dendritic cells (cDCs) are an essential immune population, responsible for controlling adaptive immunity and tolerance. Recently, type I cDCs (cDC1s) have been delineated as a distinct cDC subset, uniquely responsible for coordinating T cell-mediated immunity against pathogens and tumors. Although the importance of cDC1s is now well established, the mechanisms that regulate cDC1 function remain largely unknown. Signal Transducer and Activator of Transcription 3 (STAT3) mediates the intracellular signaling of interleukin 10 (IL-10), an immunosuppressive cytokine. Therefore, we hypothesized that STAT3 and IL-10 inhibit cDC1 function and induction of T cell-mediated immunity. Herein, we show that IL-10 inhibits polyinosinic:polycytidylic …


Enhancing Adoptive Cell Therapy By Augmenting Fitness And Anti-Tumor Function Of Tumor-Infiltrating Lymphocytes, Parin Shah 2021 The Texas Medical Center Library

Enhancing Adoptive Cell Therapy By Augmenting Fitness And Anti-Tumor Function Of Tumor-Infiltrating Lymphocytes, Parin Shah

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

The success of immune checkpoint inhibitors (ICIs) has established the importance of cancer immunotherapy in solid cancers, where it has been adopted as one of the standards of care for advanced melanoma and lung cancer. It is currently being investigated to treat other solid cancers. However, a large fraction of patients do not respond to ICIs and relapse. ICI therapy offers an in vivo approach to activate tumor-specific T cells, albeit in some cases, this modality does not create a sufficiently robust anti-tumor response. Thus, ex vivo approaches employing manipulation of immune cells, such as Adoptive Cell Therapy (ACT) using …


The Regulation Of Pannexin1 And Pannexin2 In The Skin In Health And Disease, Rafael E. Sanchez Pupo 2021 The University of Western Ontario

The Regulation Of Pannexin1 And Pannexin2 In The Skin In Health And Disease, Rafael E. Sanchez Pupo

Electronic Thesis and Dissertation Repository

Pannexins (PANX1, 2, 3) are a family of channel-forming glycoproteins that mediate intracellular and paracrine signaling. In contrast to PANX2, PANX1 has been extensively investigated in the skin, modulating cell differentiation, wound healing, and melanoma development. PANX1 and PANX2 can co-exist in the same cell and form mixed channels where their glycosylation seems to regulate their intermixing. N-glycosylation and caspase cleavage have been proposed as modulators of the function of PANX1, but their effects on PANX2 are unknown. We explored the PANX2 expression in mouse skin and showed that a Panx2 splice variant (PANX2-202) is continuously expressed throughout aging skin. …


Combination Of Oncolytic Adenoviruses, T-Cell Activation, And Blockade Of Ido Metabolic Circuitry For The Treatment Of Glioma, Teresa Nguyen 2021 The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

Combination Of Oncolytic Adenoviruses, T-Cell Activation, And Blockade Of Ido Metabolic Circuitry For The Treatment Of Glioma, Teresa Nguyen

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Glioblastoma is the most common malignant primary brain tumor in adults; the current aggressive treatment results in a 5% five-year survival rate. More effective therapies should be developed. One promising alternative is oncolytic adenovirus, Delta-24-RGD, which elicits cancer cell lysis and immunogenic cell death. In fact, Delta-24-RGD produced complete responses in 20% of recurrent glioblastoma patients through immune mechanisms that activate anti-tumor cytotoxic properties of T-cells. This cytolytic effect can further be enhanced by adding immune agonists, namely OX40L, which engages the OX40 receptor to co-stimulate activated T cells for enhanced proliferation. Hence, we produced the next generation of Delta-24-RGD, …


Intranasal Hpv Peptide Vaccine Formulation Induces Potent Cytotoxic Cd8 T Cell Immunity For The Treatment Of Genital Hpv Tumors, Gloria Sierra 2021 The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences

Intranasal Hpv Peptide Vaccine Formulation Induces Potent Cytotoxic Cd8 T Cell Immunity For The Treatment Of Genital Hpv Tumors, Gloria Sierra

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Human Papillomavirus (HPV) induced cancers continue to affect millions of women worldwide, with the five year survival rate hovering just under 60% in some demographics. Therefore there is an unmet need to develop effective, yet, easily administered therapies to treat established HPV genital lesions. Even though immune checkpoint therapy (ICT) is a promising treatment option in some HPV+ cancers, the high cost and associated toxicities are still major concerns for their widespread application. HPV cancers are textbook candidates for therapeutic vaccination intervention because they’re driven by the expression of viral oncoproteins E6 and E7, which serve as ideal tumor specific …


The Impact Of Nanopulse Treatment On The Tumor Microenvironment In Breast Cancer: Overturning The Treg Immunosuppressive Dominance, Anthony Nanajian 2021 Old Dominion University

The Impact Of Nanopulse Treatment On The Tumor Microenvironment In Breast Cancer: Overturning The Treg Immunosuppressive Dominance, Anthony Nanajian

Biomedical Sciences Theses & Dissertations

Nanopulse treatment (NPT) is a high-power electric engineering modality that has been shown to be an effective local tumor treatment approach in multiple cancer models. Our previous studies on the orthotopic 4T1-luc breast cancer model demonstrated that NPT ablated local tumors. The treatment consequently conferred protection against a second live tumor challenge and minimized spontaneous metastasis. This study aims to understand how NPT mounts a potent immune response in a predominantly immunosuppressive tumor.

NPT changed the local and systemic dynamics of immunosuppressive cells by significantly reducing the numbers of regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages …


Rapid Cell Phenotyping Using Array-Based Sensors: Applications In Cancer Stem Cell Therapy And High-Content Screening, Yingying Geng 2021 University of Massachusetts Amherst

Rapid Cell Phenotyping Using Array-Based Sensors: Applications In Cancer Stem Cell Therapy And High-Content Screening, Yingying Geng

Doctoral Dissertations

Cell surface harbors rich information regarding the status of cell health. Being able to monitor and detect its changes in response to stimuli will provide crucial information in drug discovery, disease diagnosis, and human health. Despite the efforts and breakthroughs made possible through the specific sensing approach, there are significant challenges in extracting the information on the cell surface in a quantitative and reliable way. To address this challenge, I took the approach of array-based, hypothesis-free sensing in which the engineered sensors selectively interact with target analytes, producing a distinct pattern of response that enables analyte identification. This signature-based pattern …


An Investigation Of Healthcare Supports For Those With Food Allergy In Ireland, Joseph Bolger, Nicola Blake, Sneha Vinod 2021 Munster Technological University

An Investigation Of Healthcare Supports For Those With Food Allergy In Ireland, Joseph Bolger, Nicola Blake, Sneha Vinod

International Undergraduate Journal of Health Sciences

Introduction: In Ireland, around 5% of children and 3% adults have food allergy (134,000 people). This current paper describes a survey that was carried out on a subset of service-users with the aim of identifying whether there is a need for increased specialist medical services and/or for a funded charity such as Anaphylaxis Ireland, defunct since 2015.

Materials & Methods: These needs were assessed via an online survey using Google Forms. The survey was conducted from 17-27th February 2020. There were 31 questions in total, relating to topics such as symptoms, clinical wait times, satisfaction with care provided and demand …


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