Investigate the Role of Autoantibody against Exoproteome in Cancer Patients
Date of Award
Spring 2024
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Immunobiology
First Advisor
Ring, Aaron
Abstract
Antibodies generated by humoral immune system have the capability to specifically interact withalmost any targeted antigens. Although antibodies mainly provide adaptive immunity against foreign antigens, some antibodies arise that bind to self-antigens. Typically, autoantibodies are considered for their etiologic role in mediating autoimmune diseases and can drive pathological inflammation within nearly any tissue. However, emerging research has highlighted the potential beneficial effects of certain autoantibodies in specific contexts, such as Alzheimer's disease (AD) and certain malignancies. These findings indicate that the impact of autoantibodies, whether beneficial or pathological, is contingent on the target antigen and the disease context. Antibody has a molecular weight around 150 kDa, which limits its ability to penetrate the cellmembrane. Extracellular and secreted proteins (“exoproteome”) thus represent an important group of autoantibody targets because of their accessibility. In this thesis, I investigate the role of autoantibody against human exoproteome in immunotherapy-treated cancer patients, which is enabled by a new method called REAP (rapid extracellular antigen profiling) that leverages yeast surface display to detect autoantibodies to more than 6,500 human exoproteome proteins/ peptides in a high-throughput manner. In Chapter 1, I will present a brief introduction to antibody, with a focus on the autoantibodyagainst exoproteome, particularly about its role in the disease, and explain the importance to establish an unbiased high-throughput profiling platform for autoantibody identification. In Chapter 2, I will present the detailed design rationale, developing procedures, quality control and proof-of-concept experiments of REAP method. In Chapter 3, I will show the REAP result in immunotherapy-treated cancer patients, followed by biophysical and functional characterizations of autoantibodies that have significant bias upon treatment outcomes.
Recommended Citation
DAI, YILE, "Investigate the Role of Autoantibody against Exoproteome in Cancer Patients" (2024). Yale Graduate School of Arts and Sciences Dissertations. 1359.
https://elischolar.library.yale.edu/gsas_dissertations/1359
