Please enable JavaScript or talk to your local administrator to get JavaScript enabled.
Skip filters
Skip facets
Funder
  • 40

  • 16

  • 12

  • 8

  • 8

  • 7

  • 6

  • 6

  • 5

  • 5

Funder Group
Research Organization
FOR (ANZSRC) Category
RCDC Category
Researcher
City
State
Country
Country of Funder
Start Year
Active Year
Similar Projects for

Project

Elucidating immunotherapy resistance mechanisms in non-T cell-inflamed bladder cancer

Funder: National Cancer Institute

Funding period
USD 213 K
Funding amount
Abstract
PROJECT SUMMARY Muscle invasive urothelial bladder cancer is a clinically aggressive disease with poor outcomes despite modern therapies. Recently, antibodies targeting the PD-1/PD-L1 immune checkpoint pathway have shown efficacy and were approved for use for locally advanced or metastatic bladder cancer. In some patients, impressive and durable clinical responses are observed, yet the rate of response remains modest at 20%. Mechanisms of pri- mary immune resistance in bladder cancer are not fully understood. The presence of a T cell-inflamed tumor phenotype has been associated with improved survival and response to immunotherapies. T cell-inflamed tu- mors can be identified by the presence of intratumoral CD8+ T cells or expression of a T cell gene signature. Emerging data have indicated that certain oncogenic pathways, such as FGFR3, are activated exclusively in non-T cell-inflamed bladder cancers. The underlying hypothesis of this proposal is that FGFR3 activation pre- vents spontaneous T cell priming in bladder cancer and may be therapeutically targeted to restore sensitivity to immune checkpoint blockade. A mechanistic investigation into the immunomodulatory effects of FGFR3 will be pursued through (a) a new genetically-engineered mouse model system with tamoxifen-inducible KrasG12D/p53fl/fl carcinomas that also express an activating FGFR3K644E mutation, (b) a syngeneic transplantable mouse model system using the MB49 bladder cancer cell line with model antigen expression, (c) in vitro studies examining differential gene expression in CRISPR-Cac9 derived FGFR3 knockout compared with FGFR active tumor cells, and (d) by an analysis of the immune microenvironment and FGFR3 expression in human bladder specimens using RNA in situ hybridization and multichannel immunofluorescence. The predictive capacity of these param- eters will be assessed in relation to outcomes for patients treated with anti-PD-1/L1 immunotherapy. Dr. Sweis is a physician-scientist from the University of Chicago and is the principle investigator on this study. He has devised a career development plan to obtain training in advanced tumor immunology and laboratory mouse modeling in order to facilitate his development as an independent investigator. He has developed a mentoring committee with broad expertise that is led by Dr. Thomas Gajewski, an internationally renowned expert in cancer immunology. Dr. Sweis has dedicated his efforts to the investigation of immunotherapy resistance mechanisms to improve outcomes for patients.

 
133
Projects
USD 67.1 M
Aggregated funding amount
USD 546 K
Average funding amount
Project list item
Targeting FGF in Bladder cancer after Neoadjuvant Immunotherapy and Surgery

American Association For Cancer Research to Joshua James Meeks

USD 25,000
2019 - 2020
Project list item
Combatting Bladder Cancer by Inducing Epithelial Turnover

National Cancer Institute to SOMAN N ABRAHAM

USD 203,510
2019 - 2021
Project list item
Phase 1/2 Study of Modern Immunotherapy in BCG-Relapsing Urothelial Carcinoma of the Bladder - (ADAPT-BLADDER)

National Cancer Institute to NOAH M HAHN

USD 656,816
2019 - 2024
Project list item
Defining the impact of intra-tumoral morphologic, immune and mutational heterogeneity in urothelial carcinoma

National Cancer Institute to HIKMAT AL-AHMADIE

USD 410,835
2019 - 2024
Project list item
The role of a new molecular driver in bladder cancer

National Cancer Institute to DALEY MORERA

USD 45,016
2018 - 2021
Project list item
Novel recombinant BCG for immunotherapy of bladder cancer

National Cancer Institute to BORIS SHOR

USD 290,014
2018 - 2019
Project list item
SPORE in Bladder Cancer

National Cancer Institute to DEAN F. BAJORIN, DAVID B SOLIT, MICHAEL STEPHEN GLICKMAN, TIMOTHY AN-THY CHAN, HIKMAT AL-AHMADIE, IRINA OSTROVNAYA

USD 2,299,837
2018 - 2023
Project list item
Upper tract urothelial carcinoma is non-basal and T-cell depleted

Bladder Cancer Advocacy Network to Panagiotis Vlachostergios

USD 1,700
2018 - 2018
Project list item
Role of B-arrestins in bladder cancer progression and response to chemotherapy

United States Department of Veterans Affairs to BAL L LOKESHWAR

 
2018 - 2022
Project list item
Potentiation of Immunotherapy with targeted nanoporphyrin in bladder cancer

United States Department of Veterans Affairs to CHONG-XIAN PAN

 
2018 - 2022
Project list item
Deciphering the neoantigen landscape in bladder cancer patients

Swiss National Science Foundation to Laurent Derré

USD 639,521
2018 - 2022
Project list item
Ty21a immunotherapy of non-muscle-invasive bladder cancer

Swiss National Science Foundation to Denise Nardelli Haefliger

USD 436,670
2018 - 2021
Project list item
INTRAVESICAL ONCOLYTIC THERAPY FOR BLADDER CANCER

National Cancer Institute to ROSA MARIA DIAZ, LUKKANA SUKSANPAISAN, BRADLEY C. LEIBOVICH

USD 1,081,593
2017 - 2020
Project list item
Multi-Antigen Vaccines for the Primary and Secondary Prevention of Bladder CancerTO POP: 9/15/2017 - 3/14/2019

National Cancer Institute to CLINTON GRUBBS

USD 636,313
2017 - 2019
Project list item
(PQ3) Immune epigenetic biomarkers of bladder cancer outcomes

National Cancer Institute to BROCK CLARKE CHRISTENSEN

USD 1,235,254
2017 - 2022
Project list item
Proteogenomic characterization of muscle invasive bladder cancer to identify mechanisms of resistance and targets for therapy

Bladder Cancer Advocacy Network to Seth P. Lerner, Susan Hilsenbeck, Matthew James Ellis, Keith Syson Chan, Jonathan Michael Levitt, Sung Yun Jung, Anna Malovannaya, Bing Zhang

USD 300,000
2017 - 2019
Project list item
Innate effector cells in bladder carcinogenesis

Bladder Cancer Advocacy Network to Neelam Mukherjee

USD 1,700
2017 - 2017
Project list item
Defining the translational landscape of metastatic bladder cancer and its role in therapeutic response to chemotherapy

Bladder Cancer Advocacy Network to Brian Raymond Winters

USD 1,700
2017 - 2017
Project list item
Defining the Immune Response to Chemotherapy and Chemo-Immunotherapy in Muscle-Invasive Bladder Cancer

Bladder Cancer Advocacy Network to Tracy L Rose, William Youngkwan Kim, Matthew Milowsky, Benjamin Vincent

USD 50,000
2017 - 2018
Project list item
Therapeutic Exploitation of IPSE, a Urogenital Parasite-Derived Host Modulatory Protein, for Bladder Hypersensitivity Syndromes

National Institute of Diabetes and Digestive and Kidney Diseases to MICHAEL HARRISON HSIEH

USD 1,047,708
2017 - 2022
load more...