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Exosome-based immunotherapies in ovarian cancer development of preclinical models and therapeutics / SIMONE PISANO

Swansea University Author: SIMONE PISANO

  • Redacted version - open access under embargo until: 10th October 2026

DOI (Published version): 10.23889/SUthesis.58791

Abstract

Treatment of ovarian cancer (OC) continues to present clinical challenges. It remains difficult to diagnose early stage disease, and because of this generally presents as advanced stage, with limited therapeutic options and often the development of resistance to chemotherapy. Furthermore, OC is cons...

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Published: Swansea 2021
Institution: Swansea University
Degree level: Doctoral
Degree name: Ph.D
Supervisor: Gonzalez, Deyarina; Conlan, Steven ; Corradetti, Bruna
URI: https://cronfa.swan.ac.uk/Record/cronfa58791
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first_indexed 2021-11-25T14:51:58Z
last_indexed 2021-11-26T04:17:00Z
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recordtype RisThesis
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spelling 2021-11-25T15:06:30.5304198 v2 58791 2021-11-25 Exosome-based immunotherapies in ovarian cancer development of preclinical models and therapeutics a121612db79215480a2adbc16e52e5ea SIMONE PISANO SIMONE PISANO true false 2021-11-25 Treatment of ovarian cancer (OC) continues to present clinical challenges. It remains difficult to diagnose early stage disease, and because of this generally presents as advanced stage, with limited therapeutic options and often the development of resistance to chemotherapy. Furthermore, OC is considered as an immunologically “cold” tumour based on the poor response to immunotherapies. This lack of response to immunotherapy remains poorly understood, hence better models are needed in order to elucidate the fundamental mechanisms behind tumour immunosuppression, and for new and innovative therapeutic strategies to be tested. Exosomes have recently emerged as crucial players in the cell-cell communication and content exchange within the tumour microenvironment and have also been investigated for their capacity to act as cancer therapeutics or to be re-engineered to increase their performances and effects. In this work, two main research areas were explored. The first one focused on advanced ovarian cancer modelling. Indeed, the in vitro formation of multicellular spheroids that included a mixture of cancer cells and different macrophage phenotypes was optimised, and their characteristics explored. Additionally, an in vivo advanced OC model was created from immunocompetent mice and the tumours were characterised for their immune infiltrates presence. The ascitic fluid that arose from the tumour-bearing mice was also comprehensively analysed for its immune cells content by mass cytometry for the first time in an ovarian cancer setting. The second part of the work involved the exploration of two innovative OC therapeutics. Dendritic-cell (DC) derived exosomes were obtained from tumour antigen-pulsed DCs and tested for their efficacy both in vitro and in vivo. A semi-synthetic exosomes approach was also tested by forcing monocytic cells through pores of different sizes and obtaining Immune (Cell) Derived Exosome Mimetics (IDEM). IDEM were characterised and tested in vitro on both 2D and spheroid systems. E-Thesis Swansea Exosomes, Ovarian cancer, Immunotherapy, Animal Models 25 11 2021 2021-11-25 10.23889/SUthesis.58791 A selection of third party content is redacted or is partially redacted from this thesis due to copyright restrictions.ORCiD identifier: https://orcid.org/0000-0002-5412-1241 COLLEGE NANME COLLEGE CODE Swansea University Gonzalez, Deyarina; Conlan, Steven ; Corradetti, Bruna Doctoral Ph.D Swansea University, Houston Methodist Research Institute 2021-11-25T15:06:30.5304198 2021-11-25T14:47:34.2946228 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine SIMONE PISANO 1 Under embargo Under embargo 2021-11-25T15:00:56.6646277 Output 10768033 application/pdf Redacted version - open access true 2026-10-10T00:00:00.0000000 Copyright: The author, Simone Pisano, 2021. true eng
title Exosome-based immunotherapies in ovarian cancer development of preclinical models and therapeutics
spellingShingle Exosome-based immunotherapies in ovarian cancer development of preclinical models and therapeutics
SIMONE PISANO
title_short Exosome-based immunotherapies in ovarian cancer development of preclinical models and therapeutics
title_full Exosome-based immunotherapies in ovarian cancer development of preclinical models and therapeutics
title_fullStr Exosome-based immunotherapies in ovarian cancer development of preclinical models and therapeutics
title_full_unstemmed Exosome-based immunotherapies in ovarian cancer development of preclinical models and therapeutics
title_sort Exosome-based immunotherapies in ovarian cancer development of preclinical models and therapeutics
author_id_str_mv a121612db79215480a2adbc16e52e5ea
author_id_fullname_str_mv a121612db79215480a2adbc16e52e5ea_***_SIMONE PISANO
author SIMONE PISANO
author2 SIMONE PISANO
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publishDate 2021
institution Swansea University
doi_str_mv 10.23889/SUthesis.58791
college_str Faculty of Medicine, Health and Life Sciences
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hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
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description Treatment of ovarian cancer (OC) continues to present clinical challenges. It remains difficult to diagnose early stage disease, and because of this generally presents as advanced stage, with limited therapeutic options and often the development of resistance to chemotherapy. Furthermore, OC is considered as an immunologically “cold” tumour based on the poor response to immunotherapies. This lack of response to immunotherapy remains poorly understood, hence better models are needed in order to elucidate the fundamental mechanisms behind tumour immunosuppression, and for new and innovative therapeutic strategies to be tested. Exosomes have recently emerged as crucial players in the cell-cell communication and content exchange within the tumour microenvironment and have also been investigated for their capacity to act as cancer therapeutics or to be re-engineered to increase their performances and effects. In this work, two main research areas were explored. The first one focused on advanced ovarian cancer modelling. Indeed, the in vitro formation of multicellular spheroids that included a mixture of cancer cells and different macrophage phenotypes was optimised, and their characteristics explored. Additionally, an in vivo advanced OC model was created from immunocompetent mice and the tumours were characterised for their immune infiltrates presence. The ascitic fluid that arose from the tumour-bearing mice was also comprehensively analysed for its immune cells content by mass cytometry for the first time in an ovarian cancer setting. The second part of the work involved the exploration of two innovative OC therapeutics. Dendritic-cell (DC) derived exosomes were obtained from tumour antigen-pulsed DCs and tested for their efficacy both in vitro and in vivo. A semi-synthetic exosomes approach was also tested by forcing monocytic cells through pores of different sizes and obtaining Immune (Cell) Derived Exosome Mimetics (IDEM). IDEM were characterised and tested in vitro on both 2D and spheroid systems.
published_date 2021-11-25T04:15:36Z
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score 11.016235

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