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Project

Recombinant CCL2 as a novel treatment strategy for bladder cancer

Funder: Bladder Cancer Advocacy Network

Funding period
USD 50 K
Funding amount
Abstract
Recent approval of immunotherapies has revolutionized the approach to managing bladder cancer (BC). Nevertheless, complete response is observed in only a minority of patients and there are no unambiguous biomarkers to guide treatment selection. Currently, a major obstacle in the field is limited knowledge of signals that regulate immune pathways during BC development and growth. The chemokine CCL2 (C-C motif ligand 2) is best known for its ability to induce trafficking of immune cells by binding its primary receptor, CCR2. The recruitment of immunosuppressive cells by CCL2 signaling, promotes cancer in several tumor types. In bladder, however, we show an unexpected finding that CCL2 is protective against BC development and growth. Further, we show that CCL2’s primary receptor, CCR2, is also implicated in bladder cancer defense. We hypothesize that CCL2 mediates protection against bladder tumor growth by recruiting CCR2+ T cells to the bladder environment. To address this hypothesis two specific aims are proposed. In Aim 1, we define mechanisms underlying BC protection by CCR2+ T cells. We utilize the MB49 orthotopic mouse bladder tumor model and antibody depletion studies of T cell subsets and adoptive T cell transfers to define the tumor protective roles of these CCR2+ T cells subsets. Aim 2 investigates contribution of CCL2 towards CCR2-mediated BC protection using antibody depletion of CCL2 (?CCL2) and recombinant CCL2 (rCCL2) in wildtype (WT) versus CCR2KO mice. It also tests a novel nanoparticle formulation of recombinant CCL2 to treat BC. Successful completion of this proposal will elucidate mechanisms underlying CCL2’s protection from BC growth. Data accrued from this proposal are rapidly translatable and could lead to a novel treatment strategies and/or more effective use of existing therapies for patients with BC.

 
56
Projects
USD 31.1 M
Aggregated funding amount
USD 597 K
Average funding amount
Project list item
Identifying Immunological Basis for Bladder Cancer Sex Bias

Canadian Institutes of Health Research to Hyunwoo Kwon, Zihai Li

USD 26,219
2019 - 2022
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
Elucidating immunotherapy resistance mechanisms in non-T cell-inflamed bladder cancer

National Cancer Institute to RANDY F. SWEIS

USD 425,338
2018 - 2022
Project list item
Novel recombinant BCG for immunotherapy of bladder cancer

National Cancer Institute to BORIS SHOR

USD 290,014
2018 - 2020
Project list item
Modeling bladder cancer metastasis using human patient-derived tumor organoids

Bladder Cancer Advocacy Network to Michael M Shen

USD 300,000
2018 - 2020
Project list item
Deciphering the neoantigen landscape in bladder cancer patients

Swiss National Science Foundation to Laurent Derré, Alexandre Harari, Sylvain Nguyen

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

Swiss National Science Foundation to Denise Nardelli Haefliger, Lenka Chalupova, Mathieu Chevalier, Patrice Jichlinski

USD 436,670
2018 - 2021
Project list item
Dissection of Suppressive Axes Underlying Natural Killer Cell Dysfunction in Human Bladder Cancer

Congressionally Directed Medical Research Programs to Nina Bhardwaj

USD 1,584,753
2017 - 2018
Project list item
Dissection of Suppressive Axes Underlying Natural Killer Cell Dysfunction in Human Bladder Cancer

Congressionally Directed Medical Research Programs to John Sfakianos

USD 109,710
2017 - 2018
Project list item
Investigation of the Tumor Microenvironment as a Protective Niche That Supports Treatment Resistance of Bladder Cancer

Congressionally Directed Medical Research Programs to Joshua J Meeks

USD 576,132
2017 - 2018
Project list item
Targeting the Regulation and Actions of Telomerase Reverse Transcriptase (TERT) in Bladder Cancer

Congressionally Directed Medical Research Programs to Dan Theodorescu

USD 1,482,998
2017 - 2018
Project list item
INTRAVESICAL ONCOLYTIC THERAPY FOR BLADDER CANCER

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

USD 1,990,950
2017 - 2020
Project list item
Innate effector cells in bladder carcinogenesis

Bladder Cancer Advocacy Network to Neelam Mukherjee

USD 1,700
2017 - 2017
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 1,599,959
2017 - 2022
Project list item
Defining the role of the androgen receptor low molecular weight isoforms in bladder cancer

United States Department of Veterans Affairs to MARIA MUDRYJ

 
2017 - 2020
Project list item
Facilitating immuotherapy responses in non-T cell-inflamed bladder cancer

American Association For Cancer Research to Randy F. Sweis

USD 110,000
2016 - 2018
Project list item
The Role of EZH2 in Non-Muscle Invasive Bladder Cancer

United States Department of Veterans Affairs to JOSHUA JAMES MEEKS

 
2016 - 2020
Project list item
Role of antigen-specific immunity in BCG therapy for bladder cancer

Bladder Cancer Advocacy Network to Niannian Ji, Robert Scott Svatek

USD 50,000
2016 - 2018
Project list item
Notch in bladder cancer: oncogene and tumour suppressor

Canadian Cancer Society to Peter Black, Yuzhuo Wang, Mads Daugaard, Colin Collins

USD 758,595
2016 - 2020
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
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