Strategic and Industry Partnerships
Leads: Prof. Maeve Lowery, Prof John Kennedy, Ms. Averil Power
TSJCI and the Irish Cancer Society share a vision for transforming cancer care in Ireland. The Irish Cancer Society have invested €4.5 million in several specific exemplar programmes aimed at delivering a new model of care for patients in Ireland. This unique and pioneering collaboration will embed the work of the Irish Cancer Society in TSJCI. This will be a new model showcasing how the optimal ideals of comprehensive cancer care can be developed and delivered in Ireland. By investing in the Trinity St James’s Cancer Institute (TSJCI) the Irish Cancer Society aims to accelerate the translation of cancer research into new treatments and better support for patients. The partnership will integrate Irish Cancer Society services into the hospital pathway and enhance the patient experience by ensuring better collaboration with patients across research, cancer clinical trials, clinical care and education. This significant investment by ICS will accelerate the delivery of innovation and comprehensive cancer services to patients and facilitate a long-term partnership based on a shared mission to deliver the major improvements in cancer care that our patients deserve. Evaluation and measurable results, societal impact and scalability will be an integral part of all elements of this collaboration, and ongoing evaluation mechanisms will be agreed between the Irish Cancer Society and TSJCI.
This partnership addresses an unmet need identified by the Irish Cancer Society and TSJCI, fits within a comprehensive cancer care model, and is a novel model of cancer care in Ireland, linking medicine and science.
This collaboration has several key elements:
PI(s): Prof. Maeve Lowery, Prof. Jacintha O’Sullivan and Prof. Aideen Long
Industry Partner(s): RemedyBio (Lead), aCGT Vector DAC
Funder: Disruptive Technologies Innovation Fund; 2021-2024
HEALED received €6.8m government funding as part of a 3-year programme, beginning in 2021, to develop next generation cell therapies for cancer. This consortium (TCD PIs: Prof. Aideen Long, Prof. Jacintha O’Sullivan and Prof. Maeve Lowery) will generate a pre-clinical tumour infiltrating lymphocytes (TIL) package and enable a new kind of revolutionary immunotherapy. HEALED combines the use of Remedy Biologics’ nanoreactor technology, aCGT Vector’s experience creating Good Cell Manufacturing Hubs, the patient-focused translational cancer research in TSJCI (TTMI) and University of Galway’s experience in bioinformatics (SFI Centre for Research Training in Genomics Data Science), to create a pre-clinical package on TIL therapies. TCD are specifically looking at the effects of energy metabolism, hypoxia and inflammation on the number, phenotype and migration potential of TILs in solid tumours of the ovary, breast, lung, colon, rectum, stomach, and oesophagus, and match this information with their TIL cell phenotype. This will help us understand the role of these biological processes in the tumour microenvironment and how this influences the TIL cell biology. We also aim to understand genetic changes in tumour tissues by conducting whole exome sequencing and RNA sequencing. This will be used by University of Galway to predict appropriate neoantigens in the tumours, to aid in find the most effective TILs. With the National Centre for Pharmacoeconomics (NCPE), we will investigate the expected cost effectiveness of TIL therapies from health-payers’ perspective globally.
This group brings together deep capabilities in mass-scale functional biology, GMP clinical deployment, clinical and tumour microenvironment expertise in cancer, and molecular data analytics to create a world first in near-patient, personalised, functional cancer therapeutics. HEALED brings
together an inter-disciplinary approach to generate awareness regarding the potential for TIL therapy to cure currently incurable cancers.
PIs: Prof. Jacintha O’Sullivan and Prof. Maeve Lowery
Industry Partner(s): Mirai Medical Ltd, Excelsys Technologies Ltd (now Advanced Energy)
Funder: Disruptive Technologies Innovation Fund; 2021-2024
Electroporation is the application of electric pulses to cause transient permeabilization of the cell membrane, termed reversible electroporation (rEP), allowing ions and molecules to enter the cell. Electroporation can be used for the treatment of tumours since increased membrane permeability causes chemotherapeutic drugs to enter cells, a method termed electrochemotherapy (ECT). ECT allows local cancer treatment, lowering drug dose and reducing side-effects of systemic chemotherapy. Irreversible electroporation (iEP) is an emerging cancer therapy that uses high intensity electrical pulses to ablate solid tumours. Both forms of electroporation are in use clinically. In collaboration with Mirai Medical which provides the technology (ePORE electroporator) the aim of this project is to investigate the immune response elicited by this treatment. They aim to look at the immune response in Pan GI cancer using ex vivo explants from patients in SJH. Post treatment conditioned media will be used to determine the effects of the proteomic secretome on immune cell responsiveness. This proteome will be analysed by Multiplex ELISA to determine the inflammatory profile. They will investigate the effects of electroporation on our cell line isogenic models of chemo/radio resistance to oesophageal cancer, to establish whether EP can reverse this resistance and to optimise the settings for treatment. The goal of this project is to evaluate if electroporation can be used as a combination treatment to boost treatment response in GI cancer patients.
PIs: Prof. Maeve Lowery
Industry Partner(s): Luminate Medical Ltd, Gentian Health Services
Funder: Disruptive Technologies Innovation Fund; 2023-2026
Chemotherapy-induced peripheral neuropathy (CIPN) is the loss of sensory and motor function in the fingers and toes caused by the nerve damage associated with chemotherapy treatment for cancer. CIPN is a hidden and highly debilitating side effect of cancer reatment resulting in permanent loss of hand and foot sensation, movement and function. A staggering 68% of all chemotherapy patients experience CIPN. Despite this extremely high prevalence, CIPN is also poorly diagnosed and understood clinically. Today, no preventative solution exists to protect patients from the physical disabilities caused by chemotherapy related nerve damage.
This DTIF project proposes a new solution: the LILAC suite – a smart CIPN symptom tracking app developed using new clinical knowledge in characterising CIPN progression, and the world’s first CIPN prevention device created using a new treatment technique known as Localised Microvasculature Compression Therapy. The LILAC suite (designed and manufactured in Ireland) will be first in the world designed to accurately meet the clinical need of characterising and preventing CIPN. This disruptive technology will make Ireland a world-leader in patient-centred medical devices.
PIs: Dr. Kathy Gately, Prof. Jacintha O’Sullivan and Prof. Maeve Lowery
Industry Partner(s): Legend Biotech
Funder: Legend Biotech; 2022-2023
The objective of this collaborative study is to utilize tissue samples from patients with solid tumors of great unmet need, specifically colorectal cancer (CRC), non-small cell lung cancer (NSCLC) and gastric cancer (GC) for the purpose of building an organoid platform to screen Legend Biotech’s internal pipeline candidates. Additionally, access to these samples will assist in the validation of new tumor targets by verifying upregulation of proteins expression using custom designed tumour microarrays. The collaboration aims to develop 3D models that will resemble the three tumour types for use in the discovery of new treatment targets and for screening novel CAR T-cell therapies. Through the collaboration, Legend Biotech and Trinity College hope to significantly benefit their respective research programs and improve treatment options for patients.
PI(s): Dr. Tony McElligott, Nicki Panoskaltsis, Athanasios Mantalaris, Paul Browne, Nina Orfali, Patrick Hayden
Industry Partner(s): Legend Biotech
Funder: Enterprise Ireland Innovation Partnership; 2023-2025
The objective of this collaborative study is to utilize bone marrow aspirate samples from patients with tumors of great unmet need, specifically AML and MM, for the purpose of building 3D ex-vivo modelling platforms suitable for validation of pipeline programs. This project will develop 3D bone marrow niche models to support expansion of primary AML and MM cells, from bone marrow aspirate samples. The 3D model of each patient sample will be characterised, in a collaborative effort between Legend Biotech and TCD, to assess/demonstrate preservation of the native tumor architecture and ability to support expansion and viability of patient cells. Single cell genetic profiling will determine the critical factors of the tumor microenvironment that hinder therapies. The 3D models will offer a comprehensive and scalable platform for validation of CAR-T cell candidates. The data generated will identify tumor-specific targets that are most likely to be successful in a clinical setting and will assist in the validation of tumor targets by utilising the 3D platform to screen therapies.
PI(s): Dr Cara Martin
Industry Partner(s): Roche Molecular Systems
Funder: Roche Molecular Systems; 2022-2024
PI(s): Prof. John O’Leary
Industry Partner(s): Becton Dickinson
Funder: Enterprise Ireland Innovation Partnership; 2018-2021
Circulating tumour cells (CTCs) are silent precursors of metastatic disease, that utilise various mechanisms to survive in the circulation and metastasise to distal sites. CTCs are believed to be responsible for metastatic seeding and tumour dissemination. These cells originate in the primary tumour, before extravasating and entering the peripheral circulation where they circulate amongst immune cells and erythrocytes. CTCs are highly heterogeneous (existing as single, double or clusters) and often undergo EMT, resulting in a loss of the classical epithelial detection marker, EpCAM. The biology and clinical significance of non-classical CTCs such as those lacking EpCam expression or possessing the leucocyte marker CD45 is poorly understood. In addition, CTCs are also able to aggregate forming clusters, termed circulating tumour microemboli, whose size and concentration have been found to influence the development of metastases. It is now accepted that CTC clusters have a survival advantage in the circulation, since the aggregation of the CTCs protects the tumour cells. CTCs have significant potential as clinical biomarkers in diagnosis, stratification and treatment, by facilitating early cancer detection, therapeutic target selection, real-time disease progression monitoring and real-time treatment response prediction. CTC enumeration is now considered a prognostic factor in breast, colorectal, and lung cancers. This study focussed on evaluation of a number of CTC isolation devices to enable the full repertoire of CTC forms to be isolated and characterised by single cell sequencing using the BD precise assay technology.
The research group significantly gained from the technology transfer and support from BD, underpinning the research efforts of scientists and clinicians working in the cancer ecosystem and contributing directly to the Trinity St James’s Cancer Institute, a key priority for the college. Direct links between BD and the university have been established and the group proceeding with further single cell sequencing projects using the BD Rhapsody and currently exploring further opportunities. The research has advanced our understanding of the molecular basis of cancer metastasis and enabled us to move a step closer to the clinic in order to address the unmet need that exists in cancer metastasis. The research has also allowed us to develop ex-vivo models for CTC culture, propagation and treatment testing. Our ability to grow CTCs in hypoxic conditions represents a significant step forward in technology development (TRL 3-5).
From the company perspective, it gave BD an opportunity to collaborate with world class clinical oncology researchers in order to apply the tools and methodology to CTCs. TCD and BD have built capacity around this work programme and had 2 SFI industrial fellowship grants.
As a leading global supplier, innovator and research focussed company, Becton Dickinson has a proven track record in working in collaboration with globally leading universities in the development and commercialisation of new products and processes. Interacting with high calibre scientists like the O’Leary group helped BD to drive their innovation and research forward, ensuring they are building the right products for customers.
Precision Oncology Ireland (POI) is a Science Foundation Ireland co-funded consortium of 5 Irish Universities, 6 Irish Charities, and 7 industry partners aiming to develop new diagnostics and therapeutics for personalised cancer treatment. It is an 11.9 million euro SFI Strategic Partnership.
Whole Genome and Transcriptome Sequencing of Extreme Phenotypes in Gastrointestinal Cancers
PI: Prof. Maeve Lowery
Industry Partner: Genuity Science
Personalised evaluation of the genetic signature of an individual cancer can provide both diagnostic information and enable optimal selection of therapy. However, the identification of clear predictive or prognostic biomarkers is challenging in a heterogeneous patient population. The identification and study of ‘extreme phenotype’ cancer patients can maximise the insights of genome sequencing, both in revealing the molecular causes that explain those phenotypes, and identifying useful therapeutic targets.
‘Extreme phenotype’ patients can be those with either an unusually favourable or an unusually poor prognosis, or a striking response or progression following treatment. Such patients represent real-life clinical models of drug sensitivity, resistance and toxicity, which facilitates the study of underlying molecular mechanisms. Extreme phenotype selection in cancer patients enhances the clinical interpretation of data generated by high-throughput techniques, and increases the likelihood of clinically significant discoveries. It also reduces the sample size required for informative comprehensive genome profiling, by natural enrichment of biomarker expression in patients studied, and exclusion of confounding intermediate phenotypes of uncertain significance. This project aims to identify patients with extreme GI cancer phenotypes, and perform whole genome/transcriptome sequencing on tumour and germline samples from patients. By integrating clinical information with the results of these genetic analyses, we hope to identify potential causative genetic factors and actionable therapeutic targets in these cancers. Ultimately, we are aiming to integrate genome and gene expression based clinical decision-making into the clinical routine for treating cancer patients. The project is a strategic collaboration between Trinity St James Cancer Institute (TSJCI), Genuity Science, and the British Columbia Cancer Agency (BC-CA), Canada, represented by Prof Janessa Laskin. Our collaborators at the BC-CA are leading a large Personalized OncoGenomics study since 2012, and have analysed over 1000 samples from patients with advanced refractory cancer through whole genome / transcriptome sequencing. Clinical and genetic data are presented at a multidisciplinary molecular tumour board, where clinical implications of individual patient results are reviewed and discussed. We will adopt this innovative approach and implement it in Dublin. The overall goal is to build capacity for the real time comprehensive genetic analysis of patients with extreme cancer phenotypes in Ireland, and evaluate the therapeutic implications. The National Cancer Strategy 2017-2026 clearly emphasises the need for an improvement in cancer genetics and cancer molecular diagnostic services in Ireland. Currently, clinical genetic sequencing for cancer, both germline and somatic, is limited to screens of known cancer genes either as commercial panels or at academic centres. The urgently needed capacity to functionally interpret whole genome/transcriptome sequencing of tumour biopsy samples with real time clinical and therapeutic implications does not currently exist in Ireland.
St James’s Hospital has signed a master services agreement with ICON plc, a world-leading clinical research organisation (CRO), founded and headquartered in Ireland since 1990. Working in partnership with ICON’s global Accellacare site network, the purpose of this collaboration is to enable greater access to clinical trials for cancer patients in Ireland through the TSJCI Cancer Clinical Trials Unit. ICON, as the CRO, can provide high-quality, innovative studies to TSJCI and its patients. Accellacare enables an efficient, streamlined mechanism to open studies and deliver on recruitment by offering:
(i) centralised contract negotiation with study sponsors and
(ii) supporting the delivery of the study through resourcing, such as data management and study coordination at the site.
It is a shared ambition of TSJCI and ICON to increase the number of quality clinical trials to patients in Ireland to ensure patients have access to cutting-edge treatment options that could improve and save lives. In addition, TSJCI aims to meet both national and international KPIs (NCCP and Organisation of European Cancer Institutes) and contribute to reaccreditation and designation by OECI in 2024
https://www.iconplc.com/
https://www.accellacare.com/about/
TSJCI PI/Leadership: Dr Claire Donohoe and Ms Cathy Enright
In 2022, TSJCI became the first Irish member of DIGICORE, a pan-European research network built to accelerate the implementation of precision oncology in Europe.
In 2023, TSJCI signed a partner agreement for the EISMEA approved project, DigiONE, the aim of which is to creates a federated, privacy appropriate, high quality, digital research network that links routine clinical data with routine molecular data information.