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Ty21a immunotherapy of non-muscle-invasive bladder cancer

Funder: Swiss National Science Foundation

Funding period
CHF 429 K
USD 437 K
Funding amount
Abstract
Ty21a immunotherapy of non-muscle-invasive bladder cancer1. SUMMARY Bladder cancer is the fourth and eighth most common malignancy among men and women, respectively. Seventy percent of tumors present as non muscle-invasive bladder cancer (NMIBC) at initial diagnosis with variable risk of recurrence and progression to invasive disease, thus requiring long-term surveillance. Intravesical BCG immunotherapy can reduce recurrence/progression of NMIBC, although significant adverse events and treatment failure argue for alternative options. During the ongoing granting period we have examined how another live vaccine, Vivotif®, consisting of the highly attenuated Salmonella enterica serovar Typhi strain Ty21a, used since more than 30 years against typhoid fever, may be safely used intravesically to improve bladder-tumor treatment. Our prepreclinical data demonstrate that Ty21a is more efficient than BCG at regressing established bladder tumor in the MB49-orthotopic murine model of NMBIC. This was confirmed by the ability of Ty21a to kill human tumor-cells in vitro and induce, in a novel human 3D-bladder-tissue ex-vivo assay, specific cytokines/chemokines/growth factors associated with efficient bladder-treatment. Our data confirmed a high safety, with no Ty21a bacteria persisting in mouse and human bladder tissues in contrast to BCG. Altogether, these data are of good premise for the use of the typhoid vaccine for intravesical immunotherapy of NMIBC patients.The purpose of this grant proposal is to achieve a two-steps Phase I trial with Ty21a, in order to obtain safety and immunogenicity data in patients, together with hints towards efficacy.

 
244
Projects
USD 101.0 M
Aggregated funding amount
USD 577 K
Average funding amount
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
CD40 agonism for the treatment of bladder cancer

National Cancer Institute to CHRISTOPHER STUART GARRIS

USD 64,554
2020 - 2023
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Roles of epigenetic regulators in bladder cancer progression

University of California - Cancer Research Coordinating Committee to Zhu Wang

USD 74,960
2020 - 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
Engineering Smart Solutions for Disorders of the Bladder Urothelium

Engineering and Physical Sciences Research Council

 
2019 - 2023
Project list item
Geriatric Conditions and Treatment Burden in Older Adults with Non-Muscle-Invasive Bladder Cancer and Their Caregivers

National Institute on Aging to TULLIKA GARG

USD 271,698
2019 - 2021
Project list item
Developing a SMART scaffold for bladder augmentation

National Institute of Biomedical Imaging and Bioengineering to GUILLERMO ANTONIO AMEER, ARUN SHARMA, JOHN ROGERS

USD 1,399,891
2019 - 2023
Project list item
Transdifferentiation of fibroblasts to urothelial progenitors for definitive urothelial replacement therapy in non-muscle invasive bladder cancer

Bladder Cancer Advocacy Network to Philip A Beachy, Kris Butalid Prado

USD 300,000
2019 - 2021
Project list item
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
Project list item
[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
[Efficacy and toxicity of bladder instillation of anti-tumor peptide for inhibition of bladder tumor in mice] - Original in Japanese

Japan Society for the Promotion of Science to Toru SHIMAZUI, Hiroyuki NISHIYAMA, Takahiro Kojima, Kazuhiro YOSHIKAWA

USD 39,492
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
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
Development of an automated method to capture bladder cancer recurrence and progression for epidemiologic research

National Cancer Institute to ANIKET A KAWATKAR, KIM N DANFORTH

USD 382,751
2019 - 2021
Project list item
Clonal evolution and molecular stratification of urothelial carcinoma in situ of the urinary bladder

German Research Foundation to Stefan Garczyk, Nadine Gaisa

 
2019 -
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