Life Sciences Commons^™

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 …

Functional And Phenotypical Analysis Of The Effects Of Aging On B Cells And Their Bone Marrow Microenvironment, Nicole May Ziegler

Master's Theses

Aging impacts multiple organ systems, and specifically causes the immune system to lose its ability to efficiently fight off infections. Regarding immunity, aging research predominantly focuses on the adaptive immune system. B cells, which mediate the humoral arm of the adaptive immune system, develop throughout life in the bone marrow where microenvironmental `niches' are important. The bone marrow does not exactly `atrophy' with age; however, studies comparing young and old mice demonstrate an age-related change in the bone marrow B cell subpopulations.

The overall goal was to determine if femoral and sternum bone marrow have different plasma cell composition and …