Bifidobacterium-based oral vaccine enhances anti-tumor immunity in clinical study

A novel oral vaccine platform using genetically engineered Bifidobacterium could enhance anti-tumor immunity. In an exploratory phase I clinical study, the vaccine was well tolerated and generated immunologic and clinical findings that warrant further investigation. The results also point to potential biomarkers that may help identify patients most likely to benefit from this approach.

Our immune system is naturally equipped to fight cancers. However, cancers can mutate and develop the ability to exploit the immune system's own built-in brakes - molecular off-switches called "immune checkpoints." To counter this, one modern treatment approach uses "immune checkpoint inhibitors," which work by disabling this off-switch. But cancers can develop yet other escape mechanisms and some patients don't respond to this approach at all. To boost anti-cancer immunity, researchers have tested injectable vaccines containing small fragments of a tumor-associated antigen protein called "Wilms tumor 1 (WT1) protein." However, these vaccines commonly cause local injection-site reactions and sensitize the immune system to only a limited number of WT1 features, potentially restricting the breadth of the immune response. Kobe University translational cancer researcher

Shirakawa Toshiro says: "When patients no longer respond to immune checkpoint inhibitors, effective treatment options are often limited. We need new approaches that can safely enhance anti-tumor immunity and complement immune checkpoint inhibitors."

After completing the trial, seven patients received pembrolizumab rechallenge, that is, another round of an immune checkpoint inhibitor, at their physicians' discretion. Tumor shrinkage was observed in three of these patients, all of whom had detectable WT1-specific cellular immune responses after B440 treatment. However, because of the small number of patients and the post-trial, non-randomized nature of the observation, it is not possible to determine whether B440 contributed to these responses.

The Kobe University-led team is now conducting a phase I/II clinical trial of B440 in combination with the immune checkpoint inhibitors nivolumab and ipilimumab in patients with non-removable malignant pleural mesothelioma. Shirakawa sums up the significance of the work, saying, "We believe this represents an important next step toward evaluating orally administered cancer vaccines as a new component of combination cancer immunotherapy."As this was a small, single-arm phase I trial, it was not designed to establish efficacy. These findings should therefore be regarded as exploratory and hypothesis-generating." Nevertheless, the results support further investigation of B440 in combination with, or followed by, immune checkpoint inhibitors.

Source:

Kobe University

Journal reference: