Immunotherapy Commons^™

Bacteria-Engineered Vesicles For Cancer Immunotherapy: From Immunomodulation In Vitro To Anti-Tumor Effects In Melanoma Models, Lan Li

Theses and Dissertations--Chemistry

Bacterial vesicles hold immense potential in various biomedical fields. Among these, outer membrane vesicles (OMVs) produced by Gram-negative bacteria are the most extensively studied. While the exact mechanism of OMV production remains unclear, numerous environmental factors have been shown to influence both their yield and composition. In this study, we investigated the effect of three different antimicrobial families on OMV production by E. coli. Interestingly, antimicrobials within the same family did not provide the same effects on OMV yield, suggesting that OMV production may not directly correlate with the antimicrobial mechanism of action. OMVs have demonstrated tumor-inhibitory activity in multiple …

The Critical Role Of Nac1 In Triple-Negative Breast Cancer Stemness And Immunosuppression, Chrispus Ngule

Theses and Dissertations--Toxicology and Cancer Biology

Triple-negative breast cancer (TNBC) is a highly heterogeneous and the most lethal breast cancer (BC) subtype. We report here a new role of nucleus accumbens associated protein 1 (NAC1) in maintaining stemness signature and features of TNBC and controlling the status of myeloid-derived suppressor cells, which accounts for its role in tumor progression and metastasis. This report demonstrates increased NAC1 amplification in TNBC metastatic samples compared to nonmetastatic tissues. In vitro, NAC1 depletion in TNBC cells suppressed their proliferation, colony formation, migration, and invasion. In vivo, NAC1 knockdown in TNBC cells reduced tumorigenic ability, diminished tumor growth rate, and abolished …

Delineating Contributions Of Genotype And Lineage To Lung Cancer Therapy Response, Kassandra Jo Naughton

Theses and Dissertations--Toxicology and Cancer Biology

Non-small cell lung cancer (NSCLC) heterogeneity is a major challenge for determining effective treatment strategies. Adenocarcinomas (ADCs) and squamous cell carcinomas (SCCs) are histologically and epigenetically distinct subtypes of NSCLC. Patients with ADC tumors harboring mutations in both KRAS and LKB1 (aka STK11) have lower survival rates than those with KRAS-only tumors. KRAS/LKB1 tumors are not only aggressive, but also respond poorly to immunotherapy. However, these data are limited to ADCs, and it is unclear if SCCs with this genotype are also resistant to immunotherapy. We developed a mouse model of Kras^mut/Lkb1^mut capable of producing …

Cell-Engineered Vesicles For Therapeutic Delivery And Immunomodulatory Applications, Khaga Neupane

Theses and Dissertations--Chemistry

Development of a new kind of drug delivery system (DDS) that could efficiently deliver therapeutics to the cell of interest would allow us to accomplish cell-specific drug delivery while eliminating systemic toxicity. Although nanocarriers including endogenously released extracellular vesicles (EEVs), liposomes, and small molecules seem to be promising drug delivery systems, biological challenges persist for their use in clinical applications. Here, we demonstrate nanovesicles engineered by fragmenting cellular membranes can be exploited as versatile DDSs for therapeutics delivery as well as immunomodulatory functions. Cell-engineered vesicles were produced by cavitating cells using nitrogen gas at high pressure followed by serial centrifugation. …

Mast Cells As Novel Effector Cells In The Pathogenesis Of Chronic Graft-Versus-Host Disease, Ethan Strattan

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Hematopoietic stem cell transplantation (HSCT) is most commonly a treatment for inborn defects of hematopoiesis or acute leukemias. Widespread use of HSCT, a potentially curative therapy, is hampered by onset of graft-versus-host-disease (GVHD), a condition wherein the donor cells recognize the patient tissues as non-self. GVHD can manifest anywhere from weeks to decades post-transplant and is classified as either acute or chronic GVHD, both of which are significant causes of transplant-related morbidity and mortality.

However, GVHD is a complex, multifactorial, and enigmatic disease. The factors driving GVHD at the cellular and molecular level are incompletely understood. Immunosuppression targeting T-cells has …