Using radioimmunoconjugates to target quiescent tumour cells via cancer stem cell and hypoxia-induced markers : an approach against metastatic disease and therapeutic resistance
department or school: Medicine, Faculty of
data provider: DSpace
degree campus: UBCV
creator: Law, Hin Ni
issued: 2023-01-31T08:00:00Z
issued: 2021
related degree: Master of Science - MSc
degree grantor: University of British Columbia
description: Cancer cell quiescence or dormancy is a reversible state whereby cells have undergone G0-G1 cell cycle arrest and are non-proliferating. These cells can recover the ability to self-renew with exposure to reopened or new vasculatures, and may be the founders of metastasis. One factor that may promote cancer cells to enter a dormant state is exposure to hypoxia, which not only limits cellular proliferation but also promotes drug resistance. In addition, some dormant cancer cells have been reported to express “stem-ness” markers that may provide these cells with stem cell-like characteristics to prolong survival. Thus, this thesis aims to describe work developing radioimmunoconjugates to target certain cancer stem cell and hypoxia-induced markers, specifically CD96 and carbonic anhydrase IX (CAIX), in efforts to potentially identify and eradicate dormant tumour cells, adding to the clinical arsenal against metastatic relapse and drug resistance in cancer patients. We hypothesize that leukemic stem cell- and hypoxia-specific markers can be targeted for cancer treatment and/or theranostic applications to help identify areas of tumor dormancy, aiding against drug resistance and patient relapse. Both panels of anti-CD96 and anti-CAIX radioimmunoconjugates showed specific tumour uptake in vivo for their respective target. The first aim is to evaluate radioimmunoconjugate candidates against CD96 for acute myeloid leukemia (AML) by positron emission tomography (PET) imaging, which was extensively investigated but resulted in decreasing tumour uptake over time in NRG/NSG mouse models and a loss of specific tumour uptake in the nude mouse model, suggesting a novel panel of mAbs may be required. The second aim is to screen mAbs targeting CAIX by PET imaging in renal cancer, colon cancer, and acute myeloid leukemia models, which resulted in three successful radioimmunoconjugate candidates for the solid cancers, and possible further study needed for expression of CAIX in AML. Over…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/80611
note: USING RADIOIMMUNOCONJUGATES TO TARGET QUIESCENT TUMOUR CELLS VIA CANCER STEM CELL AND HYPOXIA-INDUCED MARKERS: AN APPROACH AGAINST METASTATIC DISEASE AND THERAPEUTIC RESISTANCE by Hin Ni (Teresa) Law B.Sc., The University of British Columbia, 2018 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Interdisciplinary Oncology) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) December 2021 © Hin Ni (Teresa) Law, 2021 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the thesis entitled: Using radioimmunoconjugates to target quiescent tumour cells via cancer stem cell and hypoxia-induced markers: an approach against metastatic disease and therapeutic resistance submitted by Hin Ni (Teresa) Law in partial fulfillment of the requirements for the degree of Master of Science in Interdisciplinary Oncology Examining Committee: Dr. François Bénard, Professor, Department of Radiology, Faculty of Medicine, UBC Supervisor Dr. Urs Häfeli, Professor, Faculty of Pharmaceutical Sciences, UBC Supervisory Committee Member Dr. Kevin Hay, Assistant Professor, Division of Hematology, Faculty of Medicine, UBC Additional Examiner Additional Supervisory Committee Members: Dr. Paul Schaffer, Associate Professor, Department of Radiology, Faculty of Medicine, UBC Supervisory Committee Member iii Abstract Cancer cell quiescence or dormancy is a reversible state whereby cells have undergone G0-G1 cell cycle arrest and are non-proliferating. These cells can recover the ability to self-renew with exposure to reopened or new vasculatures, and may be the founders of metastasis. One factor that may promote cancer cells to enter a dormant state is exposure to hypoxia, which not only limits cellular proliferation but also promotes drug resistance. In addition, some dormant cancer cells have been reported to express “st…
has type: Thesis/Dissertation
date issued: 2022-05
is shown at: 10.14288/1.0406226
language: eng
degree discipline: Interdisciplinary Oncology
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
contributor: Bénard, François
type: Text
identifier URI: http://hdl.handle.net/2429/80611