The Olivia Newton-John Cancer Research Institute undertakes translational laboratory and clinical research into cancer genomics, biology, immunology, inflammation and targeted therapies, especially immunotherapy.
Immunotherapy has been heralded as the latest breakthrough in cancer treatment. This therapeutic approach of priming the body's own immune cells to destroy tumour cells has shown success in many different cancers. The Vectra multispectral immunohistochemistry platform facilitates the comprehensive analysis of each patient's cancer and its interaction with cells of the immune system, enabling better treatment selection, monitoring response, and analysis and identification of the effective approaches.
For the fewer than 10% of cancer patients who benefit from immunotherapy, long-term survival is common and as such immunotherapy is now acknowledged as a real game-changer in cancer treatment. To make treatment more widely effective, it is critical to understand the factors that distinguish response, to optimise immunotherapy based on rational approaches, resulting in long-term cancer control.
The Vectra platform is providing researchers across various research institutes with a unique tool to visualise complex cancer-immune cell interactions in each patient tumour, to detect mechanisms a tumour may use to evade the immune system and to identify biomarkers of treatment response.
Aims & Objectives
The main objective was to establish a sustainable cost recovery-based service platform to deliver high quality multispectral immunohistochemistry for research and commercial collaborations.
To this end, the Vectra system was established within the Olivia Newton-John Cancer Research Institute (ONJCRI), in collaboration with Austin Health (AH), Peter MacCallum Cancer Centre (PMCC), Victorian Comprehensive Cancer Centre (VCCC) and La Trobe Institute for Molecular Science (LIMS). These cross-disciplinary and multi-institutional collaborations have enabled knowledge transfer between different research groups and different areas of investigation.
The main objective was achieved by identifying and successfully approaching our funding partners: AH, PMCC, VCCC and LIMS. Subsequent funding from The Ian Potter Foundation then enabled equipment purchase.
In parallel, we identified and trained a research assistant and pathologist as the main operators of the system. PerkinElmer provided training of lab personnel and back-up staff.
Platform validation was undertaken using archive samples from cancer patients with known immune status, disease status and outcome. Staining and analysis protocols were established within these cohorts and a cost recovery service for research projects was created based on these protocols. Long-term sustainability has been enabled by partner usage, promotion and publications.
A Melbourne-wide Vectra user group has been established. The group involves all existing and new collaborating Institutes and meets every three months. Ongoing funding has been achieved through cost-recovery fees.
Tumour streams currently under investigation are melanoma, gastric, breast, prostate, lung, colorectal, mesothelioma, Merkel Cell Carcinoma. Additionally, we have started looking into non-Hodgkin Lymphomas.
In each the goal is to understand the nature of the immune-interactions with the tumor, which will allow us to decipher why some patients respond to immunotherapy and others not, and to identify the key elements necessary for treatment success. This may show us ways to ‘prime’ a tumor immune microenvironment in a way to render non-responsive tumors into responsive ones.
New research collaborations
Prof Sharon Lewin, Peter Doherty Institute; Dr Belinda Parker, LIMS, Dr Andreas Behren, ONJCRI
Dr. Belinda Parker and one of her PhD students are looking into the role the immune system plays in breast cancer. Dr Andreas Behren is co-supervisor assisting with the Vectra part of the project.
Dr. Nick Huntington, Walter and Eliza Hall institute, Prof. Michael Brown, Royal Adelaide Hospital Cancer Center
Dr Nick Huntington is interested in the role that NK cells have in melanoma; and Prof. Brown is interested in novel combination therapies targeting melanoma.
Prof Sharon Lewin and one of her PhD students, Ms Zuwena Richardson
This is a non-cancer project focused on ‘HIV infection immune-checkpoints’ which aims to explore the role of immune suppressive molecules in the setting of if HIV infection which may prevent the immune system from recognizing and destroying infected cells. The project uses a sophisticated combination of detection of viral DNA/RNA in combination with antibody-staining and will hopefully give us an idea how and if immune checkpoint inhibition could work in the HIV space (or other latent/chronical viral infections) to ultimately provide a cure.
These collaborative research projects demonstrate that the establishment of this technology has facilitated a variety of researchers from different areas coming together and learning from each other in order to achieve a better outcome for their respective scientific projects.
Publication & dissemination
‘Mismatch in Epitope Specificities Between IFNγ Inflamed and Uninflamed ConditionsLeads to Escape From T Lymphocyte Killing in Melanoma’. Woods et al. (2016). J Immunother Cancer 4:10, 2016.
This paper was awarded Best Basic Science Article (2015-2016), by the Society for the Immunotherapy of Cancer. It was written by Katherine Woods, a PostDoc at the ONJCRI, and used the Vectra imaging technology to explore if melanoma tumors change the way they ‘look’ to the immune system based on different molecules that can be present within the tumor microenvironment. This is an underexplored mechanism that may lead to therapy escape and, if properly understood, may be useful in designing better cancer vaccines or better anti-cancer therapeutics that include immune recognition of the cancer.
Lastly, pictures taken by Mr Candani Tutuka, ONJCRI, for various projects using the Vectra technology have been presented as part of the Day of Immunology for the last two years. This day comprises various events which are open to the general public at various venues. On these is the ‘Snapshots of the Immune System’ a photo-arts exhibition, which can still be viewed online. Feedback received from these exhibitions indicates this is a creative way to involve the general public in research and to spark interest in cutting-edge developments in medical sciences.
The project has been very successful, with increasing usage of the Vectra platform. It perfectly complements current diagnostic technologies that establish a comprehensive program to analyse how the immune system interacts with cancer. This has enabled the further development of ONJCRI as a Victorian centre of excellence for cancer-immunology, allowing it to extend its program of clinical trials and to offer unique services to other cancer centres and initiatives, including the VCCC and VCA-funded Melbourne Melanoma Project. This will lead to a better understanding of cancer, the mode of action of new therapies, and improved patient trial stratification and monitoring.
Dr Andreas Behren, Group Leader, Cancer Immunobiology Laboratory, ONJCRI
'This grant exemplifies perfectly what the Foundation looks for in projects in the Medical Research area of funding – innovation, sustainability, a strong emphasis on partnerships and, ultimately, a project that will benefit many in years to come. The Olivia Newton-John Cancer Research Institute has leveraged well the funding from the Foundation and has established a centre for excellence for cancer-immunology in Victoria.'
Dr Alberto Furlan, Senior Program Manager