Please enable JavaScript or talk to your local administrator to get JavaScript enabled.


Recombinant CCL2 as a novel treatment strategy for bladder cancer

Funder: Bladder Cancer Advocacy Network

Funding period
USD 50 K
Funding amount
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.
Similar projects All >
Sorted by: Start Date
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
Novel recombinant BCG for immunotherapy of bladder cancer

National Cancer Institute to BORIS SHOR

USD 290,014
2018 - 2019
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
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



    1107 Immunology


    1112 Oncology and Carcinogenesis

  • RCDC


  • RCDC


  • RCDC

    Urologic Diseases




    2.1 Biological and endogenous factors

  • Health Research Areas


  • Broad Research Areas

    Basic Science