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SITC 2021: Preclinical Study of Microbial Immunotherapy in Bladder Cancer

By: Julia Fiederlein
Posted: Monday, November 29, 2021

A preclinical study revealed the potential therapeutic benefit of intravesical ZH9, a live attenuated strain of Salmonella enterica Typhi, as a novel microbial immunotherapy in bladder cancer. These results, which were presented by Denise Nardelli-Haefliger, PhD, of the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, and colleagues during the 2021 Society for Immunotherapy of Cancer (SITC) Annual Meeting (Abstract 878), were also published in the Journal for ImmunoTherapy of Cancer.

“ZH9 demonstrated a significant survival benefit over the standard-of-care bacillus Calmette-Guérin [BCG] in an orthotopic bladder cancer model,” the investigators remarked. “[This therapy also] demonstrated direct tumor cell killing in vitro and induction of robust cellular immune responses in vivo.”

The investigators conducted experiments using a murine orthotopic, syngeneic MB49 bladder tumor model, and several laboratory assessments to establish the preclinical safety and efficacy of intravesical ZH9. Compared with mice treated with the vehicle (P = .003) and BCG (P < .001), those treated with a single dose of ZH9 2 days after tumor inoculation seemed to derive a significant survival benefit. In a second, stringent model setup, ZH9 appeared to demonstrate significant efficacy 4 days after tumor inoculation versus the vehicle (P = .003) and BCG (P = .025).

According to the investigators, surviving animals treated with ZH9 demonstrated 100% protection from tumor take following repeated intravesical challenge with tumor cells; this finding seemed to suggest lasting antitumor immunity. Based on in vitro intracellular flow cytometry in human (UMUC3, T24, RT4, 5637) and mouse (MB49) urothelial cancer cell lines, ZH9 seemed to invade and induce cell death. A single in vivo treatment with ZH9 demonstrated strong cellular immune responses, which were characterized by recruitment of monocytes, natural killer cells, CD4-positive and CD8-positive T cells, and dendritic cells with an activated, cross-presenting phenotype. Compared with a single equivalent dose of intravesical BCG, treatment with ZH9 resulted in a greater magnitude and duration of immune cell recruitment in the urothelium.

Disclosure: No information regarding conflicts of interest was provided.



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