Novel vaccine framework illustrates promise for oral cancer vaccines

Genetically engineered Bifidobacterium longum could enhance anti-tumour immunity, new research shows.

Leveraging a novel vaccine platform, the study by joint research team from Tokushima University, Hiroshima University and Hamamatsu University in Japan, highlight oral cancer vaccines as a new component of combination cancer immunotherapy.

Bifidobacterium was chosen due to its capacity to interact with the gut’s immune system to display a much larger portion of a modified WT1 protein.

After altering the bacterium, the team evaluated the resulting oral vaccine B440 in a Phase I trial. This involved 12 patients with metastatic urothelial cancer who had exhausted standard treatment options.

WT1-specific cellular immune responses were detected in six patients. While they previously had weak responses prior to treatment, they remained progression-free for longer than the other patients. In the remaining six patients, who had no detectable preexisting response, B440 induced a new WT1-specific immune response.

Post-trial, seven patients received an additional round of the immune checkpoint inhibitor pembrolizumab. In three of these patients, tumour shrinkage was observed. They demonstrated detectable WT1-specific cellular immune responses following B440.

Based on this data, B440 may act more as an immune enhancer than as an initiator of immunity. If this outcome is clinically confirmed, a low-level preexisting immune response to WT1 could become a biomarker candidate for those with a higher likelihood of benefitting from B440 or similar cancer immunotherapies.

Only one treatment-related adverse event was observed—a mild reaction involving a transient increase in interleukin-6 (IL-6), in three patients.

Kobe University translational cancer researcher, Shirakawa Toshiro said: “We need new approaches that can safely enhance anti-tumour immunity and complement immune checkpoint inhibitors.

“Many oral vaccines currently in use are designed to prevent infectious diseases and are based on attenuated or inactivated forms of enteric pathogens. However, developing a safe and versatile oral platform capable of delivering a selected antigen protein, such as a cancer antigen, to gut-associated lymphoid tissue remains a major challenge.”

“Developing a safe and versatile oral platform capable of delivering a selected antigen protein, such as a cancer antigen, to gut-associated lymphoid tissue remains a major challenge”

 Shirakawa Toshiro, Kobe University

However, due to the small-scale nature of the study, B440’s contribution to these responses cannot be fully verified and should be taken as “exploratory and hypothesis-generating”. Shirakawa added: “As this was a small, single-arm phase I trial, it was not designed to establish efficacy”.

Looking ahead, a Phase I/II trial of B440 is ongoing, in combination with the immune checkpoint inhibitors nivolumab and ipilimumab in non-removable malignant pleural mesothelioma.

In conclusion, according to Shirakawa, the research represents the “next step toward evaluating orally administered cancer vaccines as a new component of combination cancer immunotherapy”.

The paper was published in JCO Oncology Advances.