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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
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.

USD 101.0 M
Aggregated funding amount
USD 577 K
Average funding amount
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[Studies on a novel immunotherapy for bladder cancer by NAD+] - Original in Japanese

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