IMMUNOBIOLOGY AND IMMUNOTHERAPY OF CANCER
Grant number: 1132373 | Funding period: 2018 - 2022
For 60 years, we have had only 3 effective cancer treatments: surgery, radiation and chemotherapy, often used in combination.The last 5 years have produced a powerful fourth treatment: the patient's own immune system.The long standing collaborations and synergies of our multi-disciplinary teams have already underpinned many recent advances in immune-based therapies: we are now poised to develop several further immunotherapies and on track to test them in patients during the term of this grant.
Related publications (21)
A Histone Deacetylase Inhibitor, Panobinostat, Enhances Chimeric Antigen Receptor T-cell Antitumor Effect Against Pancreatic Cancer.
Aesha I Ali, Minyu Wang, Bianca von Scheidt, Pilar M Dominguez, Aaron J Harrison, Daniela Gm Tantalo, Jian Kang, Amanda J Oliver, Jack D Chan, Xin Du, Yuchen Bai, Belinda Lee, Ricky W Johnstone, Phillip K Darcy, Michael H Kershaw, Clare Y Slaney
PURPOSE: In this article, we describe a combination chimeric antigen receptor (CAR) T-cell therapy that eradicated the majority of..
Early-phenotype CAR-T cells for the treatment of pediatric cancers.
D Meyran, RL Terry, JJ Zhu, M Haber, DS Ziegler, PG Ekert, JA Trapani, PK Darcy, PJ Neeson
Chimeric antigen receptor (CAR)-T-cell therapy is a promising approach for the treatment of childhood cancers, particularly high-r..
MAIT cells regulate NK cell-mediated tumor immunity
Emma Petley, Hui-Fern Koay, Melissa A Henderson, Kevin Sek, Kirsten L Todd, Simon P Keam, Junyun Lai, Imran G House, Jasmine Li, Magnus Zethoven, Amanda XY Chen, Amanda J Oliver, Jessica Michie, Andrew J Freeman, Lauren Giuffrida, Jack D Chan, Angela Pizzolla, Jeffrey YW Mak, Timothy R McCulloch, Fernando Souza-Fonseca-Guimaraes
The function of MR1-restricted mucosal-associated invariant T (MAIT) cells in tumor immunity is unclear. Here we show that MAIT ce..
CRISPR/Cas9 mediated deletion of the adenosine A2A receptor enhances CAR T cell efficacy
Lauren Giuffrida, Kevin Sek, Melissa A Henderson, Junyun Lai, Amanda XY Chen, Deborah Meyran, Kirsten L Todd, Emma Petley, Sherly Mardiana, Christina Molck, Gregory D Stewart, Benjamin J Solomon, Ian A Parish, Paul J Neeson, Simon J Harrison, Lev M Kats, Imran G House, Phillip K Darcy, Paul A Beavis
Adenosine is an immunosuppressive factor that limits anti-tumor immunity through the suppression of multiple immune subsets includ..
Generating CAR T cells from tumor-infiltrating lymphocytes.
Jane K Mills, Melissa A Henderson, Lauren Giuffrida, Pasquale Petrone, Jennifer A Westwood, Phillip K Darcy, Paul J Neeson, Michael H Kershaw, David E Gyorki
Background: Tumor-infiltrating lymphocytes (TILs) and chimeric antigen receptor (CAR) T-cell therapies have demonstrated promising..
IL-15 Preconditioning Augments CAR T Cell Responses to Checkpoint Blockade for Improved Treatment of Solid Tumors
Lauren Giuffrida, Kevin Sek, Melissa A Henderson, Imran G House, Junyun Lai, Amanda XY Chen, Kirsten L Todd, Emma Petley, Sherly Mardiana, Izabela Todorovski, Emily Gruber, Madison J Kelly, Benjamin J Solomon, Stephin J Vervoort, Ricky W Johnstone, Ian A Parish, Paul J Neeson, Lev M Kats, Phillip K Darcy, Paul A Beavis
Chimeric antigen receptor (CAR) T cell therapy has been highly successful in hematological malignancies leading to their US Food a..
Macrophage-Derived CXCL9 and CXCL10 Are Required for Antitumor Immune Responses Following Immune Checkpoint Blockade
Imran G House, Peter Savas, Junyun Lai, Amanda XY Chen, Amanda J Oliver, Zhi L Teo, Kirsten L Todd, Melissa A Henderson, Lauren Giuffrida, Emma V Petley, Kevin Sek, Sherly Mardiana, Tuba N Gide, Camelia Quek, Richard A Scolyer, Georgina V Long, James S Wilmott, Sherene Loi, Phillip K Darcy, Paul A Beavis
PURPOSE: Response rates to immune checkpoint blockade (ICB; anti-PD-1/anti-CTLA-4) correlate with the extent of tumor immune infil..
PTPN2 phosphatase deletion in T cells promotes anti-tumour immunity and CAR T-cell efficacy in solid tumours
Florian Wiede, Kun-Hui Lu, Xin Du, Shuwei Liang, Katharina Hochheiser, Garron T Dodd, Pei K Goh, Conor Kearney, Deborah Meyran, Paul A Beavis, Melissa A Henderson, Simone L Park, Jason Waithman, Sheng Zhang, Zhong-Yin Zhang, Jane Oliaro, Thomas Gebhardt, Phillip K Darcy, Tony Tiganis
Although adoptive T-cell therapy has shown remarkable clinical efficacy in haematological malignancies, its success in combating s..
High dose-rate brachytherapy of localized prostate cancer converts tumors from cold to hot
Simon P Keam, Heloise Halse, Thu Nguyen, Minyu Wang, Nicolas Van Kooten Losio, Catherine Mitchell, Franco Caramia, David J Byrne, Sue Haupt, Georgina Ryland, Phillip K Darcy, Shahneen Sandhu, Piers Blombery, Ygal Haupt, Scott G Williams, Paul J Neeson
BACKGROUND: Prostate cancer (PCa) has a profoundly immunosuppressive microenvironment and is commonly immune excluded with few inf..
Enterotoxins can support CAR T cells against solid tumors
Bianca von Scheidt, Minyu Wang, Amanda J Oliver, Jack D Chan, Metta K Jana, Aesha I Ali, Fiona Clow, John D Fraser, Kylie M Quinn, Phillip K Darcy, Michael H Kershaw, Clare Y Slaney
Responses of solid tumors to chimeric antigen receptor (CAR) T cell therapy are often minimal. This is potentially due to a lack o..
Genetic Redirection of T Cells for the Treatment of Pancreatic Cancer
Aesha I Ali, Amanda J Oliver, Tinaz Samiei, Jack D Chan, Michael H Kershaw, Clare Y Slaney
Conventional treatments for pancreatic cancer are largely ineffective, and the prognosis for the vast majority of patients is poor..
Switching on the green light for chimeric antigen receptor T-cell therapy
Sherly Mardiana, Junyun Lai, Imran Geoffrey House, Paul Andrew Beavis, Phillip Kevin Darcy
Adoptive cellular therapy involving genetic modification of T cells with chimeric antigen receptor (CAR) transgene offers a promis..
Tissue-specific tumor microenvironments influence responses to immunotherapies
Amanda J Oliver, Ashleigh S Davey, Simon P Keam, Sherly Mardiana, Jack D Chan, Bianca von Scheidt, Paul A Beavis, Imran G House, Jonas RM Van Audernaerde, Phillip K Darcy, Michael H Kershaw, Clare Y Slaney
Objectives: Investigation of variable response rates to cancer immunotherapies has exposed the immunosuppressive tumor microenviro..
Single-cell profiling of breast cancer T cells reveals a tissue-resident memory subset associated with improved prognosis
Peter Savas, Balaji Virassamy, Chengzhong Ye, Agus Salim, Christopher P Mintoff, Franco Caramia, Roberto Salgado, David J Byrne, Zhi L Teo, Sathana Dushyanthen, Ann Byrne, Lironne Wein, Stephen J Luen, Catherine Poliness, Sophie S Nightingale, Anita S Skandarajah, David E Gyorki, Chantel M Thornton, Paul A Beavis, Stephen B Fox
The quantity of tumor-infiltrating lymphocytes (TILs) in breast cancer (BC) is a robust prognostic factor for improved patient sur..