Engineering B Cells For Use In Immunotherapy and Cancer

<p>B cells can be divided into effector and regulatory immune cells. While effector B cells are key drivers of humoral immunity due to their ability to generate antibodies specific to pathogens, regulatory B cells (Bregs) have recently been shown to control inflammatory responses in multiple diseases through the production of anti-inflammatory cytokines, including interleukin (IL)-10, IL-35 and transforming growth factor-beta (TGF-b). Ex vivo expansion of B cells has been challenging due to their tendency to undergo apoptosis in culture. Thus, creating a successful expansion protocol with exceptional viability will open the door for B cells to be used directly for adoptive therapy or as a source of antibody production ex vivo. Furthermore, a strategy to preferentially expand Bregs may be an attractive approach to mitigate autoimmune disorders and graft-versus-host disease. The primary goal of this thesis project is to understand factors that skew B cell function and to develop a protocol for the expansion of Bregs with immunomodulatory properties for cell therapy. We hypothesized that using genetic engineering tools we can skew the function of B cells toward a suppressive phenotype and support their ex vivo proliferation and survival to generate a viable subset of Bregs for cell therapy. We successfully generated B cells that displayed suppressive capabilities and used mass cytometry to characterize their phenotype. However, the immunoregulatory function of B cells was transient. Interrogation of the expanded B cells at the single cell level revealed multiple markers that could potentially be modified to maintain the suppressive capacity of the in vitro expanded B cells for future cell therapy application</p>

Name thesis:degree_name

Masters of Science (MS)

Level thesis:degree_level

Thesis (MS)

Year dc:date.available

2021

Authors dc:creator

• Ensley, Emily
• <p>https://orcid.org/0000-0003-4212-2260</p>

Contributors dc:contributor

• Katayoun Rezvani, M.D. Ph.D.
• Richard Eric Davis, M.D.
• Vahid Afshar-Khargan, M.D.

• b cells
• Immunotherapy
• Regulatory B cells
• T cells
• Bregs
• CytoF
• cell therapy
• Medicine and Health Sciences

Repository record dc:identifier

https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1074

OAI identifier oai:identifier

oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-2131