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Potentiation of Immunotherapy with targeted nanoporphyrin in bladder cancer

Funder: United States Department of Veterans Affairs

Funding period
Funding amount
ABSTRACT Bladder cancer (BCa) is one of the most common cancers in veterans. There is no significant improvement in overall survival for advanced BCa over the last three decades. Immunotherapy with immune checkpoint inhibitors showed promising anti-tumor activity in this disease. However, less than 20% of patients respond to this treatment. Various strategies, including combination with other therapies, are being explored to enhance the efficacy of immunotherapy. With the funding of the VA Career Development Award-2 and VA Merit, we developed a BCa-specific PLZ4-nanoporphyrin (PNP) that combines imaging-guided chemotherapy, photodynamic and photothermal therapies into a single platform. All three therapies have been shown to potentiate immunotherapy with cancer vaccines. Here we propose to determine whether the efficacy of immunotherapy with an immune checkpoint inhibitor can be enhanced via combining immunotherapy with chemotherapy, photodynamic and photothermal therapies using PNP. Because PNP can target the mouse BCa cell line MB49, we will first conduct the efficacy studies in immunocompetent mice carrying MB49 syngeneic tumors. Recently, we developed humanized mice in which the immune cells of the host mice are derived from humans. We will implant into these mice patient-derived xenografts (PDX) that are developed from unselected and uncultured human patient cancer tissues in order to validate the MB49 cell line studies in mice. We will then translate the studies into BCa transgenic mice to determine whether PNP can potentiate immunotherapy. Mechanisms of resistance will also be studied. Since we have already held a pre-IND (Investigational New Drug) consultation with the US Food and Drug Administration for PNP, successful completion of this project can lead to a clinical trial to combine PNP with immunotherapy in BCa.

USD 63.8 M
Aggregated funding amount
USD 874 K
Average funding amount
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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
CD40 agonism for the treatment of bladder cancer

National Cancer Institute to CHRISTOPHER STUART GARRIS

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

National Cancer Institute to ANDREW TRUONG

USD 45,016
2020 - 2023
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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 -
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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
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Bladder cancer chemotherapy potentiation with a multiprong arachidonic acid pathway modulator

National Cancer Institute to PAUL THOMAS HENDERSON

USD 300,000
2019 - 2020
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Recombinant CCL2 as a novel treatment strategy for bladder cancer

Bladder Cancer Advocacy Network to Neelam Mukherjee, Robert Scott Svatek

USD 50,000
2019 - 2020
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[Studies on a novel immunotherapy for bladder cancer by NAD+] - Original in Japanese

Japan Society for the Promotion of Science to 博史 上原, Haruhito AZUMA, Kazumasa Komua

USD 39,508
2019 - 2024
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
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
Efficacy of immunotherapy in the first and second line treatment of metastatic bladder cancer

German Research Foundation to Philipp Dahm, Philipp Maisch

2019 -
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Urinary microbiota characterization of superficial bladder Cancer patients undergoing BCG immunotherapy

São Paulo Research Foundation to Anamaria Aranha Camargo

2018 - 2022
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
SPORE in Bladder Cancer


USD 4,438,686
2018 - 2023
Project list item
Targeting TAM (Tyro3-Axl-Mer) family of transmembrane receptor tyrosine kinases in bladder cancer.

Bladder Cancer Advocacy Network to Arpita Roy

USD 1,700
2018 - 2018
Project list item
Novel Biomarkers for the Clinical Management of Bladder Cancer

National Cancer Institute to VINATA B LOKESHWAR

USD 902,622
2018 - 2023
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