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Full-Text Articles in Immunology and Infectious Disease
The Characterization Of T-Cell Manufacturing For Adoptive T-Cell Therapies, Amir Alpert
The Characterization Of T-Cell Manufacturing For Adoptive T-Cell Therapies, Amir Alpert
Dissertations & Theses (Open Access)
Adoptive T-cell therapy using genetically modified T cells has emerged as a potential therapeutic option for several malignancies. Central to the production of the cellular therapy is the manufacturing using a stimulation, genetic engineering, and expansion methodology. Within this framework, there is a delicate balance between expansion of the cells to a therapeutically relevant dosage and the need to retain the proliferative potential of the ‘living drug’. I show that as T-cells are expanded for elongated periods of time, they lose their proliferative potential and become functionally senescent despite the presence of multiple proliferative cytokines. In addition, I show that …
Enhancing Immunotherapeutic Interventions For Treatment Of Chronic Lymphocytic Leukemia, Kamira K. Maharaj
Enhancing Immunotherapeutic Interventions For Treatment Of Chronic Lymphocytic Leukemia, Kamira K. Maharaj
USF Tampa Graduate Theses and Dissertations
Chronic lymphocytic leukemia (CLL) is the most common leukemia in developed countries. It is characterized by the accumulation of CD5+ B lymphocytes in the peripheral blood, bone marrow, and lymphoid tissues of affected patients. Patients experience lymphadenopathy, fatigue, and are severely immunocompromised. Management of disease and symptoms is possible with chemo-immunotherapy for higher risk patients; however, CLL remains incurable unless bone marrow transplant is performed. Identification of novel targets and optimization of current therapeutics is therefore still necessary. The new targeted therapies are at the forefront of development for CLL treatment, but it remains challenging to maximize their efficacies while …
Structure-Guided T Cell Receptor Mutations That Alter Antigen Specificity, Cross-Reactivity, And Polyfunctional Phenotypes In Gene-Modified T Cells, Kendra Foley
Dissertations
Adoptive cell transfer of T cell receptor (TCR) gene-modified T cells targeting specific tumor antigens is currently in clinical trials for patients with advanced malignancies. Despite the clinical responses, there are still hurdles to be overcome in achieving an effective and safe therapy. One of the limitations in the success of this type of therapy is the potential for cross-reactivity and unanticipated off-target reactivity which could lead to autoimmunity. Adverse events encompassing these "off-target, off-tumor" cross-reactivities leading to autoimmunity have been seen in patients in different clinical trials. Here, we demonstrate a novel approach to improve antigen specific reactivity and …