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Project

Defining the Immune Response to Chemotherapy and Chemo-Immunotherapy in Muscle-Invasive Bladder Cancer

Funder: Bladder Cancer Advocacy Network

Funding period
USD 50 K
Funding amount
Abstract
Neoadjuvant chemotherapy (NAC) is the standard of care for muscle-invasive bladder cancer (MIBC), but despite this aggressive care, over half of patients eventually relapse and die from their disease. Several immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway have recently been FDA approved in the treatment of metastatic bladder cancer, and immunotherapy trials and combination chemo-immunotherapy trials are underway. It is therefore critical to identify the potential immunomodulatory effects of chemotherapy to inform the development of chemo-immunotherapy combinations. Our lab (among others) has previously identified two molecular subtypes of high-grade, MIBC, termed “luminal” and “basal.” We have evidence that a subset of luminal tumors, which at baseline have a paucity of inflammation and immune checkpoint expression, become more heavily immune infiltrated after NAC. We hypothesize that NAC is eliciting an antigen-driven immune response and we aim to evaluate the effect of NAC on the intratumoral and peripheral blood T cell receptor (TCR) repertoire. In addition, previous studies have suggested that a subset of luminal tumors may be more sensitive to treatment with immune checkpoint inhibition. We hypothesize that the addition of immunotherapy to NAC will potentiate the antigen-driven immune response in luminal tumors. To answer these questions, we will study the dynamic response of the immune microenvironment and the peripheral blood in a subtype-specific manner after cytotoxic chemotherapy alone and combination chemo-immunotherapy via our ongoing biospecimen acquisition protocol and our UNC-led, multicenter phase II trial of neoadjuvant pembrolizumab, gemcitabine, and cisplatin followed by radical cystectomy in MIBC. These studies will assist the development and optimization of chemo-immunotherapy combinations in MIBC to ultimately improve the cure rate of a deadly disease.

 
147
Projects
USD 71.9 M
Aggregated funding amount
USD 631 K
Average funding amount
Project list item
Intravesical delivery of an Fc-enhanced CD40 agonist antibody for the treatment of bladder cancer

Bladder Cancer Advocacy Network to Jeffrey Ravetch, David Knorr

USD 300,000
2020 - 2022
Project list item
Epigenetic regulators of subtype plasticity in bladder cancer

Bladder Cancer Advocacy Network to John Robert Christin

USD 1,700
2020 - 2020
Project list item
Targeting regulatory B cells (Bregs) to improve anti-bladder cancer immunity

Bladder Cancer Advocacy Network to Burles Avner Johnson, David McConkey

USD 50,000
2020 - 2021
Project list item
Dissecting myeloid cell-mediated resistance to immune checkpoint blockade in bladder cancer

National Cancer Institute to NINA BHARDWAJ, JUN ZHU, MATTHEW GALSKY

USD 703,400
2020 - 2025
Project list item
Implication of neutrophil extracellular traps in the efficacy of bladder-sparing therapy in muscle invasive bladder cancer

Canadian Institutes of Health Research to Wassim Kassouf, Ciriaco A. Piccirillo, Jonathan David Spicer

USD 138,878
2020 - 2025
Project list item
CD40 agonism for the treatment of bladder cancer

National Cancer Institute to CHRISTOPHER STUART GARRIS

USD 64,554
2020 - 2023
Project list item
Effect of APOBEC3 on Bladder Cancer Biology and Response to Immunotherapy

National Cancer Institute to ANDREW TRUONG

USD 45,016
2020 - 2023
Project list item
Analysis of the antineoplastic action of Class I HDAC inhibitors to define new combination therapies for urothelial carcinoma

German Research Foundation to Günter Niegisch, Michèle Janine Hoffmann

 
2020 -
Project list item
Chemotherapy plus PD-1 blockade as bladder-sparing treatment for muscle-invasive bladder cancer

V Foundation for Cancer Research to Matthew D Galsky

USD 600,000
2019 - 2022
Project list item
Unravelling Mechanisms of Resistance to Checkpoint Inhibition in Canine Urothelial Carcinoma

V Foundation for Cancer Research to Nicola J. Mason

USD 500,000
2019 - 2021
Project list item
Engineering Smart Solutions for Disorders of the Bladder Urothelium

Engineering and Physical Sciences Research Council

 
2019 - 2023
Project list item
Bladder cancer chemotherapy potentiation with a multiprong arachidonic acid pathway modulator

National Cancer Institute to PAUL THOMAS HENDERSON

USD 300,000
2019 - 2020
Project list item
Investigating underlying molecular mechanisms of epigenetic therapies in muscle-invasive bladder cancer

Bladder Cancer Advocacy Network to Swathi Ramakrishnan

USD 1,700
2019 - 2019
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
Biomarker-Based Tools for Treatment Response Decision Support of Bladder Cancer

National Cancer Institute to LUBOMIR M HADJIYSKI, AJJAI SHIVARAM ALVA

USD 1,278,655
2019 - 2024
Project list item
Refined phenotyping and personalized targeting of muscle-invasive bladder cancer

Swiss National Science Foundation to Roland Seiler, Vera Genitsch, Marianna Kruithof-de Julio, Federico La Manna, Martina Minoli, Kiu Yan Charlotte Ng, Franziska Singer, Eugenio Zoni

USD 709,398
2019 - 2023
Project list item
Combatting Bladder Cancer by Inducing Epithelial Turnover

National Cancer Institute to SOMAN N ABRAHAM

USD 372,404
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 1,313,632
2019 - 2024
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