Life Sciences Commons^™

Developing Novel Approaches To Improve Response To T Cell Based Cancer Immunotherapy, Rina M. Mbofung

Dissertations & Theses (Open Access)

Recently, T cell based immunotherapies have moved to the forefront of cancer immunotherapy with the success of Adoptive T cell therapy (ACT) and Immune checkpoint blockade.ACT, where patients are treated with tumour infiltrating T cells (TILs), conferred a clinical response rate of ~50%. Treatment with anti-CTLA4 and anti –PD1 therapy, conferred response rates of up to 50%, greatly improving the overall survival of patients with advanced melanoma amongst other cancer types. Despite the encouraging outcomes, there are relatively low response rates coupled with the delay of weeks to months before tumour shrinkage can be appreciated. Thus, understanding what tumour intrinsic …

Plasmacytoid Dendritic Cell-Mediated Humoral Autoimmunity, Stephanie M. Dorta-Estremera Ph.D.

Dissertations & Theses (Open Access)

Humoral autoimmunity is characterized by the breakdown of B cell immune tolerance to self-antigens and consequent production of pathogenic autoantibodies. Plasmacytoid dendritic cells (pDCs), a potent type I interferon (IFN-I) producer, have been linked to the pathogenesis of systemic lupus erythematosus (SLE), a prototypic systemic humoral autoimmune disease. However, the cellular events that stimulate the development of humoral autoimmunity as a result of pDC activation have not been characterized. Moreover, the B cell subset(s) responsible for the generation of autoantibodies remains to be clearly identified.

The immunization of DNA-containing amyloids into non-autoimmune mice triggers the activation of pDCs and induction …

Determining The Mechanisms Generating Soluble Il-15 Complexes, Scott Anthony

Dissertations & Theses (Open Access)

A diverse assortment of infectious pathogens and TLR agonists enhance the expression of Interleukin (IL)-15. Additionally, inducing lymphopenia enhances anti-tumor responses in an IL-15-dependent manner. Paradoxically, despite the limited expression of IL-15 during homeostasis, the role of IL-15 during the steady state is well-known, while its roles during inflammation and infections remain largely undefined. IL-15 uses a unique method of production and presentation to support the development and homeostasis of NK and CD8 T cells. IL-15 is produced with its high affinity IL-15Rα and this IL-15Rα/IL-15 complex is shuttled to the cell surface where it is presented in-trans or cleaved …