Copper ionophores as inducers of immunogenic cell death : a mechanistic and therapeutic evaluation
department or school: Medicine, Faculty of
data provider: DSpace
degree campus: UBCV
creator: Heroux, Devon Travis
issued: 2025-10-22T23:43:06Z
issued: 2025
related degree: Doctor of Philosophy - PhD
degree grantor: University of British Columbia
description: Immunotherapy, particularly immune checkpoint inhibition (ICI), has transformed cancer treatment and led to durable responses in subsets of patients. However, response rates remain low across many tumour types, and strategies to improve ICI efficacy are urgently needed. Metal-based chemotherapies, such as platinum (Pt)-containing agents like cisplatin and oxaliplatin, have long been used in oncology. Although oxaliplatin induces ICD, its systemic toxicity and inconsistent benefit in combination with ICI have limited its clinical applicability. Copper (Cu), unlike Pt, is a bioessential trace element required for mitochondrial respiration and redox regulation. These cellular processes are frequently upregulated in Cu-enriched tumour cells to support proliferation and metastasis. Historically, Cu chelation has been explored as a way to deprive tumour cells of this essential nutrient. More recently, an alternative strategy has emerged: delivering Cu therapeutically to induce a form of regulated cell death known as cuproptosis. This mechanism, and its potential to enhance anticancer immunity, remains underexplored in the context of immunotherapy. This thesis presents a systematic investigation of Cu in anticancer immunity, focusing on both therapeutic delivery and the influence of baseline Cu levels in the tumour microenvironment (TME). A liposomal formulation of the Cu complex of diethyldithiocarbamate (Cu(DDC)â) was developed and shown to activate adaptive immune responses in syngeneic mouse tumour models. A comparative screen of Cu-binding compounds revealed that the ability to transport Cu intracellularly (ionophore-like activity) was associated with ICD induction. Although both Cu(DDC)â and a Cu complexation of clioquinol (Cu(CQ)â) activated ICD markers, they elicited distinct transcriptional responses, suggesting compound-specific effects on cell death and immune activation. To assess the influence of baseline Cu content, CT26 and MC38 tumour models were characteri…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/92714
note: Copper Ionophores as Inducers of Immunogenic Cell Death: A Mechanistic and Therapeutic Evaluation by Devon Travis Heroux MSc, McGill University, 2012 BSc (H), University of British Columbia, 2009 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in The Faculty of Graduate and Postdoctoral Studies (Interdisciplinary Oncology) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) October 2025 © Devon Travis Heroux, 2025ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the dissertation entitled: Copper Ionophores as Inducers of Immunogenic Cell Death: A Mechanistic and Therapeutic Evaluation. submitted by Devon Travis Heroux in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Interdisciplinary Oncology Examining Committee: Marcel Bally, Professor, Pathology and Laboratory Medicine, UBC Supervisor Julian Lum, Professor, Biochemistry and Microbiology, University of Victoria Supervisory Committee Member Karla Williams, Associate Professor, Pharmaceutical Sciences, UBC University Examiner David Schaeffer, Associate Professor, Pathology and Laboratory Medicine, UBC University Examiner John Bell, Professor, Medicine, University of Ottawa External Examiner Additional Supervisory Committee Member: Mads Daugaard, Associate Professor, Urologic Sciences, UBC Supervisory Committee Member iii Abstract Immunotherapy, particularly immune checkpoint inhibition (ICI), has transformed cancer treatment and led to durable responses in subsets of patients. However, response rates remain low across many tumour types, and strategies to improve ICI efficacy are urgently needed. Metal-based chemotherapies, such as platinum (Pt)-containing agents like cisplatin and oxaliplatin, have long been used in oncology. Although oxaliplatin induces ICD, its systemic toxicity and inconsistent benefit in combination with ICI have limited its …
has type: Thesis/Dissertation
date issued: 2026-05
is shown at: 10.14288/1.0450537
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: Bally, Marcel B., 1956-
type: Text
identifier URI: http://hdl.handle.net/2429/92714