First Oral Cancer Vaccine Using Bacterial Vector Shows Safety and Immune Response in Metastatic Urothelial Cancer Phase I Trial

17 Jul First Oral Cancer Vaccine Using Bacterial Vector Shows Safety and Immune Response in Metastatic Urothelial Cancer Phase I Trial

Prof. Shirakawa

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Shirakawa: Immune checkpoint inhibitors have significantly improved the treatment of metastatic urothelial cancer, but many patients eventually develop resistance, leaving limited therapeutic options. We developed B440, a first-in-human oral cancer vaccine using genetically engineered Bifidobacterium longum expressing the WT1 tumor-associated antigen, with the goal of enhancing tumor-specific cellular immunity through the gut immune system.

In this phase I study, B440 demonstrated a favorable safety profile with no dose-limiting toxicities. WT1-specific cellular immune responses were detected in half of the patients, and these patients showed a trend toward longer progression-free survival. As this was a small, single-arm phase I study, these findings should be considered exploratory and hypothesis-generating. For context on how immune checkpoint inhibitors have reshaped the treatment landscape for metastatic urothelial cancer, see this earlier overview of immunotherapy in the treatment of metastatic urothelial cancer.

MedicalResearch.com: Might this vehicle be suitable for other types of cancer vaccine?

Dr. Shirakawa: Potentially, yes. One of the important features of this platform is that the Bifidobacterium-based oral delivery system may be adaptable to other tumor-associated antigens by replacing the expressed antigen. Therefore, this vehicle could potentially serve as a broader oral antigen-delivery platform for cancer vaccines, although each new antigen would require careful preclinical and clinical evaluation.

In addition, B440 itself targets WT1, which is expressed in multiple cancer types. Therefore, B440 may also be applicable to other WT1-expressing malignancies beyond urothelial cancer. We are currently conducting a phase I/II study of B440 in combination with immune checkpoint inhibitors in patients with unresectable malignant pleural mesothelioma, another cancer type in which WT1 is considered a relevant antigen.

MedicalResearch.com: What should readers take away from your report?

Dr. Shirakawa: Our study provides the first clinical evidence that this oral bacterial vector platform can be safely administered to patients and can induce antigen-specific cellular immune responses. Rather than demonstrating definitive clinical efficacy, this study establishes a foundation for further development of oral cancer vaccines.

An additional point is that exploratory, off-study observations after B440 treatment suggested possible clinical activity when immune checkpoint blockade was reintroduced in some patients. However, this was not part of the trial protocol and should be interpreted with caution. These findings support the need for prospectively designed trials evaluating B440 in combination with immune checkpoint inhibitors.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Dr. Shirakawa: Future studies should evaluate B440 in larger, controlled clinical trials, particularly in combination with immune checkpoint inhibitors. The ongoing phase I/II trial in unresectable malignant pleural mesothelioma is one such effort to investigate whether B440 can enhance antitumor immunity when combined with immune checkpoint blockade.

Further research should also examine predictive biomarkers, including WT1-specific cellular immune responses and gut microbiome changes, to identify patients most likely to benefit from this approach. In parallel, the platform concept should be explored with other tumor-associated antigens to determine whether oral bacterial antigen delivery can be extended to other cancer vaccine strategies.

MedicalResearch.com: Is there anything else you would like to add? Any disclosures?

Dr. Shirakawa: I would like to express my sincere gratitude to all patients who participated in this investigator-initiated trial, as well as to the physicians, clinical research coordinators, and all collaborators who made this study possible.

Disclosure: Dr. Shirakawa is the founder and CEO of Immunorock Co., Ltd., which is developing the B440 platform. This relationship is fully disclosed in the published article.

Citation:
Hideto Ueki et al. Phase I Study of B440, an Oral Wilms’ Tumor 1 Cancer Vaccine Using a Bifidobacterium Vector, in Patients With Metastatic Urothelial Cancer. JCO Oncol Adv 3, e2500153 (2026). DOI: 10.1200/OA-25-00153

Disclaimer: The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Some links are sponsored. Products, services and providers are not warranted or endorsed by MedicalResearch.com or Eminent Domains Inc. Always seek the advice of your physician or other qualified health provider and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website.

Last Updated on July 17, 2026 by Marie Benz MD FAAD