Targeting Adenosine Mediated Immunosuppression to Enhance Car T Cell Activity in Breast Cancer

A2AR eGFP reporter mouse enables elucidation of A2AR expression dynamics during anti-tumor immune responses

Kirsten L Todd, Junyun Lai, Kevin Sek, Yu-Kuan Huang, Dane M Newman, Emily B Derrick, Hui-Fern Koay, Dat Nguyen, Thang X Hoang, Emma V Petley, Cheok Weng Chan, Isabelle Munoz, Imran G House, Joel N Lee, Joelle S Kim, Jasmine Li, Junming Tong, Maria N. de Menezes, Christina M Scheffler, Kah Min Yap

2023-11-01

There is significant clinical interest in targeting adenosine-mediated immunosuppression, with several small molecule inhibitors h..

Cellular networks controlling T cell persistence in adoptive cell therapy

JD Chan, J Lai, CY Slaney, A Kallies, PA Beavis, PK Darcy

2021-12-01

The antitumour activity of endogenous or adoptively transferred tumour-specific T cells is highly dependent on their differentiati..

CRISPR/Cas9 mediated deletion of the adenosine A2A receptor enhances CAR T cell efficacy

L Giuffrida, K Sek, MA Henderson, J Lai, AXY Chen, D Meyran, KL Todd, EV Petley, S Mardiana, C Mølck, GD Stewart, BJ Solomon, IA Parish, PJ Neeson, SJ Harrison, LM Kats, IG House, PK Darcy, PA Beavis

2021-12-01

Adenosine is an immunosuppressive factor that limits anti-tumor immunity through the suppression of multiple immune subsets includ..

CDK4/6 inhibition promotes antitumor immunity through the induction of T-cell memory

EJ Lelliott, IY Kong, M Zethoven, KM Ramsbottom, LG Martelotto, D Meyran, JJ Zhu, M Costacurta, L Kirby, JJ Sandow, L Lim, PM Dominguez, I Todorovski, NM Haynes, PA Beavis, PJ Neeson, ED Hawkins, GA McArthur, IA Parish, RW Johnstone

2021-10-01

Pharmacologic inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6) are an approved treatment for hormone receptor–positive brea..

Myeloma natural killer cells are exhausted and have impaired regulation of activation

C D'Souza, SP Keam, HXA Yeang, M Neeson, K Richardson, AK Hsu, R Canfield, N Bezman, M Robbins, H Quach, DS Ritchie, SJ Harrison, JA Trapani, HM Prince, PA Beavis, PK Darcy, PJ Neeson

2021-09-01

Not available.

The role of exhaustion in CAR T cell therapy

GM Delgoffe, C Xu, CL Mackall, MR Green, S Gottschalk, DE Speiser, D Zehn, PA Beavis

2021-07-12

CAR T cell therapy successes are challenged by several mechanisms of resistance including the development of dysfunctional states ..

IL-15 Preconditioning Augments CAR T Cell Responses to Checkpoint Blockade for Improved Treatment of Solid Tumors

L Giuffrida, K Sek, MA Henderson, IG House, J Lai, AXY Chen, KL Todd, EV Petley, S Mardiana, I Todorovski, E Gruber, MJ Kelly, BJ Solomon, SJ Vervoort, RW Johnstone, IA Parish, PJ Neeson, LM Kats, PK Darcy, PA Beavis

2020-11-04

Chimeric antigen receptor (CAR) T cell therapy has been highly successful in hematological malignancies leading to their US Food a..

Targeting the epigenetic regulation of antitumour immunity

SJ Hogg, PA Beavis, MA Dawson, RW Johnstone

2020-11-01

Dysregulation of the epigenome drives aberrant transcriptional programmes that promote cancer onset and progression. Although defe..

Intratumoral copper modulates PD-L1 expression and influences tumor immune evasion

F Voli, E Valli, L Lerra, K Kimpton, F Saletta, FM Giorgi, D Mercatelli, JRC Rouaen, S Shen, JE Murray, A Ahmed-Cox, G Cirillo, C Mayoh, PA Beavis, M Haber, JA Trapani, M Kavallaris, O Vittorio

2020-10-01

Therapeutic checkpoint antibodies blocking programmed death receptor 1/programmed death ligand 1 (PD-L1) signaling have radically ..

Adoptive cellular therapy with T cells expressing the dendritic cell growth factor Flt3L drives epitope spreading and antitumor immunity

J Lai, S Mardiana, IG House, K Sek, MA Henderson, L Giuffrida, AXY Chen, KL Todd, EV Petley, JD Chan, EM Carrington, AM Lew, BJ Solomon, JA Trapani, K Kedzierska, M Evrard, SJ Vervoort, J Waithman, PK Darcy, PA Beavis

2020-08-01

Adoptive cell therapies using genetically engineered T cell receptor or chimeric antigen receptor T cells are emerging forms of im..

Tissue-resident memory T cells in breast cancer control and immunotherapy responses

A Byrne, P Savas, S Sant, R Li, B Virassamy, SJ Luen, PA Beavis, LK Mackay, PJ Neeson, S Loi

2020-06-01

The presence of tumour-infiltrating lymphocytes (TILs) is associated with favourable outcomes in patients with breast cancer as we..

Efficient CRISPR/Cas9 gene editing in uncultured naive mouse T cells for in vivo studies

S Nü Ssing, IG House, CJ Kearney, AXY Chen, SJ Vervoort, PA Beavis, J Oliaro, RW Johnstone, JA Trapani, IA Parish

2020-04-15

CRISPR/Cas9 technologies have revolutionized our understanding of gene function in complex biological settings, including T cell i..

Sex-specific adipose tissue imprinting of regulatory T cells

A Vasanthakumar, D Chisanga, J Blume, R Gloury, K Britt, DC Henstridge, Y Zhan, SV Torres, S Liene, N Collins, E Cao, T Sidwell, C Li, RG Spallanzani, Y Liao, PA Beavis, T Gebhardt, N Trevaskis, SL Nutt, JD Zajac

2020-03-26

Adipose tissue is an energy store and a dynamic endocrine organ^1,2. In particular, visceral adipose tissue (VAT) is cri..

Macrophage-derived CXCL9 and CXCL10 are required for antitumor immune responses following immune checkpoint blockade

IG House, P Savas, J Lai, AXY Chen, AJ Oliver, ZL Teo, KL Todd, MA Henderson, L Giuffrida, EV Petley, K Sek, S Mardiana, TN Gide, C Quek, RA Scolyer, GV Long, JS Wilmott, S Loi, PK Darcy, PA Beavis

2020-01-15

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

F Wiede, KH Lu, X Du, S Liang, K Hochheiser, GT Dodd, PK Goh, C Kearney, D Meyran, PA Beavis, MA Henderson, SL Park, J Waithman, S Zhang, ZY Zhang, J Oliaro, T Gebhardt, PK Darcy, T Tiganis

2020-01-15

Although adoptive T-cell therapy has shown remarkable clinical efficacy in haematological malignancies, its success in combating s..

An Evolutionarily Conserved Function of Polycomb Silences the MHC Class I Antigen Presentation Pathway and Enables Immune Evasion in Cancer

ML Burr, CE Sparbier, KL Chan, YC Chan, A Kersbergen, EYN Lam, E Azidis-Yates, D Vassiliadis, CC Bell, O Gilan, S Jackson, L Tan, SQ Wong, S Hollizeck, EM Michalak, HV Siddle, MT McCabe, RK Prinjha, GR Guerra, BJ Solomon

2019-10-14

Loss of MHC class I (MHC-I) antigen presentation in cancer cells can elicit immunotherapy resistance. A genome-wide CRISPR/Cas9 sc..

Antagonism of IAPs enhances CAR T-cell efficacy

J Michie, PA Beavis, AJ Freeman, SJ Vervoort, KM Ramsbottom, V Narasimhan, EJ Lelliott, N Lalaoui, RG Ramsay, RW Johnstone, J Silke, PK Darcy, I Voskoboinik, CJ Kearney, J Oliaro

2019-02-01

Chimeric antigen receptor (CAR) T-cell therapy has proven successful in the treatment of hematological malignancies, notably acute..

CAR T cells take centre stage

PA Beavis, PK Darcy

2019-01-01

Switching on the green light for chimeric antigen receptor T-cell therapy

S Mardiana, J Lai, IG House, PA Beavis, PK Darcy

2019-01-01

Adoptive cellular therapy involving genetic modification of T cells with chimeric antigen receptor (CAR) transgene offers a promis..

Dual PD-1 and CTLA-4 Checkpoint blockade promotes antitumor immune responses through CD4 þ FOXP3 – cell–mediated modulation of CD103 þ dendritic cells

PA Beavis, MA Henderson, L Giuffrida, AJ Davenport, EV Petley, IG House, J Lai, K Sek, N Milenkovski, LB John, S Mardiana, CY Slaney, JA Trapani, S Loi, MH Kershaw, NM Haynes, PK Darcy

2018-09-01

Immunotherapy is widely accepted as a powerful new treatment modality for the treatment of cancer. The most successful form of imm..

Single-cell profiling of breast cancer T cells reveals a tissue-resident memory subset associated with improved prognosis

P Savas, B Virassamy, C Ye, A Salim, CP Mintoff, F Caramia, R Salgado, DJ Byrne, ZL Teo, S Dushyanthen, A Byrne, L Wein, SJ Luen, C Poliness, SS Nightingale, AS Skandarajah, DE Gyorki, CM Thornton, PA Beavis, SB Fox

2018-07-01

The quantity of tumor-infiltrating lymphocytes (TILs) in breast cancer (BC) is a robust prognostic factor for improved patient sur..

Tumor-derived exosomes modulate T cell function through transfer of RNA

IG House, EV Petley, PA Beavis

2018-03-01

Tumor cells can develop a variety of mechanisms to evade and subvert the immune system for their survival. Bland et al., in this e..

Chimeric antigen receptor T cells form nonclassical and potent immune synapses driving rapid cytotoxicity

AJ Davenport, RS Cross, KA Watson, Y Liao, W Shi, HM Prince, PA Beavis, JA Trapani, MH Kershaw, DS Ritchie, PK Darcy, PJ Neeson, MR Jenkins

2018-02-27

Chimeric antigen receptor T (CAR-T) cells are effective serial killers with a faster off-rate from dying tumor cells than CAR-T ce..

Tumor immune evasion arises through loss of TNF sensitivity

CJ Kearney, SJ Vervoort, SJ Hogg, KM Ramsbottom, AJ Freeman, N Lalaoui, L Pijpers, J Michie, KK Brown, DA Knight, V Sutton, PA Beavis, I Voskoboinik, PK Darcy, J Silke, JA Trapani, RW Johnstone, J Oliaro

2018-01-01

Immunotherapy has revolutionized outcomes for cancer patients, but the mechanisms of resistance remain poorly defined. We used a s..

Agonist immunotherapy restores T cell function following MEK inhibition improving efficacy in breast cancer

S Dushyanthen, ZL Teo, F Caramia, P Savas, CP Mintoff, B Virassamy, MA Henderson, SJ Luen, M Mansour, MH Kershaw, JA Trapani, PJ Neeson, R Salgado, GA McArthur, JM Balko, PA Beavis, PK Darcy, S Loi

2017-12-01

The presence of tumor-infiltrating lymphocytes in triple-negative breast cancers is correlated with improved outcomes. Ras/MAPK pa..

A Novel Target Antigen for the Treatment of Acute Myeloid Leukemia by CAR T Cells

PA Beavis, K Sek, PK Darcy

2017-09-06

A novel combination strategy for effectively targeting cancer stem-like cells

PA Beavis, EV Petley, PK Darcy

2017-08-01

A multifunctional role for adjuvant anti-4-1BB therapy in augmenting antitumor response by chimeric antigen receptor T cells

S Mardiana, LB John, MA Henderson, CY Slaney, B Von Scheidt, L Giuffrida, AJ Davenport, JA Trapani, PJ Neeson, S Loi, NM Haynes, MH Kershaw, PA Beavis, PK Darcy

2017-03-15

Adoptive immunotherapy utilizing chimeric antigen receptor (CAR) T cells has demonstrated high success rates in hematologic cancer..

Targeting the adenosine 2A receptor enhances chimeric antigen receptor T cell efficacy

PA Beavis, MA Henderson, L Giuffrida, JK Mills, K Sek, RS Cross, AJ Davenport, LB John, S Mardiana, CY Slaney, RW Johnstone, JA Trapani, J Stagg, S Loi, L Kats, D Gyorki, MH Kershaw, PK Darcy

2017-03-01

Chimeric antigen receptor (CAR) T cells have been highly successful in treating hematological malignancies, including acute and ch..