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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.

 
106
Projects
USD 48.7 M
Aggregated funding amount
USD 553 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
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
CD40 agonism for the treatment of bladder cancer

National Cancer Institute to CHRISTOPHER STUART GARRIS

USD 64,554
2020 - 2023
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
[The association between SORL1 and advanced bladder cancer] - Original in Japanese

Japan Society for the Promotion of Science to Takanobu UTSUMI

USD 26,335
2019 - 2021
Project list item
Identifying Immunological Basis for Bladder Cancer Sex Bias

Canadian Institutes of Health Research to Hyunwoo Kwon, Zihai Li

USD 45,605
2019 - 2022
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
Defining the impact of intra-tumoral morphologic, immune and mutational heterogeneity in urothelial carcinoma

National Cancer Institute to HIKMAT AL-AHMADIE

USD 821,670
2019 - 2024
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
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, Alexandre Harari, Sylvain Nguyen

USD 642,703
2018 - 2022
Project list item
Ty21a immunotherapy of non-muscle-invasive bladder cancer

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

USD 437,441
2018 - 2021
Project list item
Studying the Effect of PPARG Pathway Modulation on Tumor Immune Microenvironment in Muscle Invasive Bladder Cancer

Congressionally Directed Medical Research Programs to Shruti D Shah

USD 262,050
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
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
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