NEW STRATEGIES FOR ENHANCING CHIMERIC ANTIGEN RECEPTOR (CAR) T CELL THERAPY FOR CANCER
Grant number: 1136680 | Funding period: 2018 - 2022
The role of the immune system in cancer is now recognised as highly important, highlighted by the success of immunotherapy in patients. Yet many patients fail to respond to this form of treatment due to low frequency of lymphocytes present at the tumor site. A new form of immunotherapy involving transfer of gene-modified lymphocytes is a potential way to overcome this problem. This project will explore new strategies to enhance the utility of this approach against blood and solid cancers.
Related publications (15)
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..
Cellular networks controlling T cell persistence in adoptive cell therapy
Jack D Chan, Junyun Lai, Clare Y Slaney, Axel Kallies, Paul A Beavis, Phillip K Darcy
The antitumour activity of endogenous or adoptively transferred tumour-specific T cells is highly dependent on their differentiati..
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..
Pharmacological and genetic strategies for targeting adenosine to enhance adoptive T cell therapy of cancer
Kevin Sek, Lev M Kats, Phillip K Darcy, Paul A Beavis
Adoptive cellular therapy involves the ex vivo expansion of immune cells, conventionally T cells, before reinfusion back to the pa..
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..
Enhancing chimeric antigen receptor T-cell immunotherapy against cancer using a nanoemulsion-based vaccine targeting cross-presenting dendritic cells
Jack D Chan, Bianca von Scheidt, Bijun Zeng, Amanda J Oliver, Ashleigh S Davey, Aesha Ali, Ranjeny Thomas, Joseph A Trapani, Phillip K Darcy, Michael H Kershaw, Riccardo Dolcetti, Clare Y Slaney
Objectives: Adoptive transfer of chimeric antigen receptor (CAR)-modified T cells is a form of cancer immunotherapy that has achie..
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..
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..
Enumeration, functional responses and cytotoxic capacity of MAIT cells in newly diagnosed and relapsed multiple myeloma
Nicholas A Gherardin, Liyen Loh, Lorenztino Admojo, Alexander J Davenport, Kelden Richardson, Amy Rogers, Phillip K Darcy, Misty R Jenkins, H Miles Prince, Simon J Harrison, Hang Quach, David P Fairlie, Katherine Kedzierska, James McCluskey, Adam P Uldrich, Paul J Neeson, David S Ritchie, Dale I Godfrey
Mucosal-associated invariant T (MAIT) cells are T cells that recognise vitamin-B derivative Ag presented by the MHC-related-protei..