Medical Immunology Commons^™

The Systemic Quantification Of Immune Cell Populations In Various Murine Models: How Age, Tumor Burden, And Immunotherapy Affect The Immune Response, Kavita Sinha

Honors Scholar Theses

Immunotherapy as a form of cancer treatment has become increasingly popular in the past few decades. Researchers have worked to figure out how to best use the body’s natural defense mechanism, the immune system, to fight off and destroy cancer cells. In particular, the goal has been to manipulate checkpoint blockades such as CTLA-4 and PD-1 in order to take the breaks off of the immune system, allowing for a prolonged immune response to the cancer. This work has led to the development of human versions of anti-CTLA4 antibodies (ipilimumab, tremelimumab) and anti-PD1 antibodies (pembrolizumab and Nivolumab) that are currently …

The Effect Of K562-Il21-2 Plasma Membrane Particles On The Proliferation Of Natural Killer Cells To Fight Cancer, Michelle Prophete

Honors Undergraduate Theses

Immunotherapy has emerged as a current and future paradigm of cancer treatment, which utilizes the body’s immune system to eradicate cancer. Natural Killer (NK) cells as part of the innate immune system have immense potential in their anti-tumor cytotoxic activities and host cell surveillance properties. NK cells comprise approximately five to fifteen percent of peripheral blood lymphocytes and can be proliferated in vitro using recently developed methods with co-cultures with feeder cells (derived from engineered tumor cells) or plasma membrane (PM) particles, produced from the fore mentioned feeder cells, in combination with soluble cytokines. For efficient growth and maintenance of …

Challenges Of Adoptive (T-)Cell Transfer Immunotherapy For Cancer, Aaron Volk

Biology: Student Scholarship & Creative Works

Background and significance: The rebirth of the theory of immunosurveillance in 2001 rejuvenated interest in anticancer immunotherapies. In particular, T-cell-based therapies have garnered substantial interest due to the robustness and tumor antigen-specific cytotoxicity of T-cell anticancer immune responses.

Hypothesis: The efficacy of adoptive cell transfer (ACT) T-cell immunotherapy could significantly improve and gain widespread approval if future innovations in ACT-based approaches account for the pro- and antitumoral properties of non-CD8⁺ lineages of effector T-cells, evasion of T-cell antitumor immunity, and tumor-induced suppression of antitumor immunity.

Problem Analysis: Despite numerous reports of highly successful ACT-based clinical trials, no such therapy …

A Requirement For Y841 In Jak3 Enzymatic Activity And Hematopoietic Cancers, George Steven Martinez

Open Access Theses & Dissertations

A medical need exists for successfully treating people afflicted with leukemia, especially those who develop drug resistant forms. Relapse leukemia cases are particularly high within Hispanic populations where this disease is among the most frequently occurring cancer. Fourteen somatic mutations have been reported in Janus tyrosine kinase 3 (Jak3), including M511I and A573V, from patients with various forms of leukemia. To monitor drug sensitivity, a model system was developed. Indeed, many of these mutations have been shown to possess transforming ability in cell lines such as the IL-3 dependent pro-B cell line Ba/F3. As such, Ba/F3 cells were transformed to …

Immunomodulation Of Myeloid-Derived Suppressor Cells By Particulate B-Glucan In Cancer., Sabrin Husein Albeituni

Electronic Theses and Dissertations

Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells that promote tumor progression. In this study, we investigated the effect of dectin-1 stimulation by yeast-derived particulate β-glucan in MDSC function and differentiation in cancer. In vivo treatment of mice bearing lewis lung carcinoma and mammary cell carcinoma with particulate β-glucan decreased tumor weight and splenomegaly, and reduced the accumulation of polymorphonuclear-MDSC (PMN-MDSC) but not monocytic-MDSC (M-MDSC) in the spleen and tumor. In addition, particulate β-glucan differentially modulated the function of different MDSC subsets; it enhanced PMN-MDSC respiratory burst and apoptosis, and induced the differentiation of M-MDSC into …

Killer Cell Activation By A Novel Multifunctional Protein: An Immuno/Gene Therapy For Cancer, Ashlee Tietje

All Dissertations

One of the characteristics of advanced tumors is the evasion of the immune system. There are multiple methods that tumor cells employ to achieve this including reducing the expression of activating ligands on the cell surface and a shift in the tumor microenvironment toward pro-tumor cytokines. The purpose of this research is to develop a novel bifunctional fusion protein that will target these two deficiencies in the tumor microenvironment and activate killer cells that are already present. The proposed protein combines the extracellular domain of a ligand for the killer cell activating receptor NKG2D and Interleukin-12 (IL-12). It is hypothesized …

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

University Scholar Projects

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

Honors Scholar Theses

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

Paracrine Apoptotic Effect Of P53 Mediated By Tumor Suppressor Par-4, Ravshan Burikhanov, Tripti Shrestha-Bhattarai, Nikhil Hebbar, Shirley Qiu, Yanming Zhao, Gerard P. Zambetti, Vivek M. Rangnekar

Radiation Medicine Faculty Publications

The guardian of the genome, p53, is often mutated in cancer and may contribute to therapeutic resistance. Given that p53 is intact and functional in normal tissues, we harnessed its potential to inhibit the growth of p53-deficient cancer cells. Specific activation of p53 in normal fibroblasts selectively induced apoptosis in p53-deficient cancer cells. This paracrine effect was mediated by p53-dependent secretion of the tumor suppressor Par-4. Accordingly, the activation of p53 in normal mice, but not p53⁻/⁻ or Par-4⁻/⁻ mice, caused systemic elevation of Par-4, which induced apoptosis of p53-deficient tumor cells. Mechanistically, p53 …

Nkg2d Ligands In Cancer, Neha Das Gupta

Theses and Dissertations (ETD)

NK cell transplantation has been increasingly used to treat cancers that are resistant to chemotherapy. However, not all cancers are susceptible to NK cell killing. The prevalence and mechanisms of NK cell resistance have not been well elucidated. Because NKG2D is a major activating receptor on NK cells, we sought to test the hypothesis that NKG2D is the primary pathway in tumor cell recognition. Herein, we comprehensively assessed 20 cancer cell lines representing a broad array of cancer types. In line with our primary hypothesis, no cancer cell lines that expressed low levels of NKG2D ligands were susceptible to NK …

Phase Ii Evaluation Of Dasatinib In The Treatment Of Recurrent Or Persistent Epithelial Ovarian Or Primary Peritoneal Carcinoma: A Gynecologic Oncology Group Study., Russell J Schilder, William E Brady, Heather A Lankes, James V Fiorica, Mark S Shahin, Xun C Zhou, Robert S Mannel, Harsh B Pathak, Wei Hu, R Katherine Alpaugh, Anil K Sood, Andrew K Godwin

Department of Medical Oncology Faculty Papers

OBJECTIVES: Preclinical data suggest an important role for the sarcoma proto-oncogene tyrosine kinase (SRC) in the oncogenesis of epithelial ovarian cancer (EOC) or primary peritoneal carcinoma (PPC). The Gynecologic Oncology Group (GOG) conducted a Phase II trial to evaluate the efficacy and safety of dasatinib, an oral SRC-family inhibitor in EOC/PPC, and explored biomarkers for possible association with clinical outcome.

METHODS: Eligible women had measurable, recurrent or persistent EOC/PPC and had received one or two prior regimens which must have contained a platinum and a taxane. Patients were treated with 100mg orally daily of dasatinib continuously until progression of disease …

Altered Leptin Signaling On Dendritic Cells As A Potential Mechanism For Cancer Immunotherapy, Lorena Y. De Los Santos

Open Access Theses & Dissertations

Leptin is a pleiotropic hormone synthesized primarily by white adipocytes and its receptors are expressed in a variety of tissues and cells such as in the hypothalamus and cells of the immune system. Multiple cell types can produce a considerable amount of leptin such as skeletal muscle, placenta, and osteoblasts to name a few and its synthesis has been shown to be regulated by sex hormones and a broad range of inflammatory mediators. Although leptin has been shown to directly affect immune response, we are interested in how leptin affects dendritic cell function and their ability to induce a proper …