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Similar Projects for

Project

Modulation of regulatory T cells in the bladder tumor environment by anti-PD-L1 immunotherapy

Funder: Bladder Cancer Advocacy Network

Funding period
USD 50 K
Funding amount
Abstract
Immunotherapies, specifically checkpoint inhibitors blocking PD ligand-1 (PD-L1) and its inhibitory receptor PD-1, lead to durable responses in a minority of patients with platinum-refractory and platinum-naïve bladder transitional cell carcinoma (TCC), and improved survival in the platinum-refractory setting. However, the features that predict responses, and the immune populations in TCC that are responsible for benefit with anti-PD-1/PD-L1, remain obscure. This proposal addresses the novel hypothesis that anti-PD-L1 modulates the activity of regulatory T cells (Tregs), which we and others have described in TCC, and addresses the following Specific Aims: 1. Does anti-PD-L1 therapy reduce the abundance of Tregs, including in specific spatial microenvironments associated with TCC tumors? 2. Does anti-PD-L1 therapy change the antigenic repertoire of Tregs in TCC? These Aims will be addressed using samples, specifically pre-treatment biopsies and immunotherapy-treated cystectomy specimens, from patients with localized TCC treated with neoadjuvant atezolizumab (anti-PD-L1) before cystectomy as part of an ongoing clinical trial, as well as patients from a companion cohort of non-immunotherapy-treated TCC patients (standard of care). Aim 1 addresses effects of anti-PD-L1 on Treg number and distribution via flow cytometric and immunohistochemical comparison of atezolizumab-treated cystectomies and either paired pre-treatment biopsies or standard of care cystectomies. Aim 2 uses T cell receptor (TCR) sequencing of Tregs from atezolizumab-treated and standard of care cystectomies as well as paired pre-treatment biopsies, to understand how anti-PD-L1 modulates Treg TCR repertoire diversity as well as the frequency of specific Treg clonotypes. This will reveal novel roles for Tregs in responsiveness to anti-PD-L1 in TCC, leading to avenues for therapeutic targeting of Tregs or enhancement of immune responses to specific tumor antigens that are suppressed by Tregs.

 
59
Projects
USD 25.8 M
Aggregated funding amount
USD 496 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
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
Ultrasound-based diagnostic and monitoring of bladder cancer treatment with drug released from nanoparticles

National Cancer Institute to JOE ASSOULINE, YI LUO

USD 350,240
2018 - 2020
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
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
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
Development of personalized surgical algorithms for muscle-invasive bladder cancer patients

National Cancer Institute to PHILIP ABBOSH

USD 437,828
2017 - 2019
Project list item
Identifying Genomic Determinants of Chemoradiotherapy Response in Muscle-Invasive Bladder Cancer

Bladder Cancer Advocacy Network to Kent William Mouw, Alan D'Andrea, Jason Efstathiou, Anthony John Iafrate

USD 50,000
2016 - 2018
Project list item
Determinants of T-Cell Activity in Bladder Cancer

Congressionally Directed Medical Research Programs to Vivek K Arora

USD 549,000
2015 - 2016
Project list item
Non-invasive quantification of microcirculation heterogeneity as a biomarker for the diagnosis and response prediction of bladder cancer

Bladder Cancer Advocacy Network to Huyen Thanh Nguyen

USD 1,700
2015 - 2015
Project list item
Insulin resistance in the development and progression of invasive bladder cancer

National Cancer Institute to RONAC MAMTANI

USD 697,560
2015 - 2020
Project list item
Immunotherapy of human bladder cancer

National Cancer Institute to LAWRENCE FONG

USD 1,767,276
2015 - 2020
Project list item
Detection of COX-2-expressing bladder cancer by fluorocoxib A

National Cancer Institute to MARIA CEKANOVA

USD 414,939
2014 - 2018
Project list item
Using orthotopic MB49/C57 mice model to delineate the prophylactic activity of Ganoderma lucidum in bladder transitional cell carcinoma

University Grants Committee to Yuen Wai-man John, Chan Shu Yin Eddie, Gohel Mayur Danny Indulal, Law Ka Wai Helen, Ng Chi-fai

USD 78,421
2014 - 2017
Project list item
Regulatory T cells in intravesical BCG therapy for non-muscle invasive bladder cancer

Japan Society for the Promotion of Science to Mitsuhiro NARITA, Eiki Hanada, 亮介 村井, Akihiro KAWAUCHI, Kazumasa OGASAWARA, Susumu KAGEYAMA, Tatsuhiro YOSHIKI

USD 45,237
2014 - 2017
Project list item
Targeting the MET pathway in urothelial carcinoma

National Cancer Institute to ANDREA APOLO

USD 3,393,436
2014 - 2018
Project list item
Mechanisms underlying dampening of the immune response in non-muscle invasive bladder cancer (NMIBC)

Swiss National Science Foundation to Laurent Derré, Patrice Jichlinski

USD 319,918
2013 - 2016
Project list item
Efficacy of BCG Therapy is a Function of Bladder Tumor Immune Microenvironment

National Cancer Institute to JAMES JOSEPH LEE

USD 391,738
2013 - 2015
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