Some brain tumors remain incurable even after surgery, radiation, and chemotherapy and are often linked to a short life expectancy. To explore a potential new therapy, researchers analyzed long-term data from an earlier brain tumor vaccine trial to determine whether the treatment was associated with longer survival and improved tumor control.

The original trial enrolled 33 adults with newly diagnosed astrocytoma, a brain tumor named for its resemblance to astrocytes, star-shaped cells that help support nerve cells by supplying nutrients and maintaining a healthy environment around them. Their tumors were classified as grade III or IV under the 2007 World Health Organization system, meaning they had features linked to more aggressive disease. Every tumor also carried the same mutation in IDH1, a gene involved in cell metabolism that is often altered in adult astrocytomas. The mutation changes the IDH1 protein, creating an abnormal protein fragment that is present in the tumor but not in healthy cells. The vaccine takes advantage of that alteration. It contains a synthetic version of this abnormal protein fragment, which researchers hoped would train the immune system to recognize tumor cells carrying the mutation. Thirty-two participants received at least one vaccine dose as part of a schedule of eight injections over about six months following diagnosis, in addition to radiation, chemotherapy, or both. Of those participants, 30 provided enough blood samples for researchers to analyze their immune responses.

• Eight years after diagnosis, 66% of the treated participants were still alive, while 42% had survived without tumor growth or recurrence.
  
• Among the 11 participants with grade IV tumors, median survival (the point at which half were still alive) was about 8.8 years, compared with roughly 2.6 to 4.7 years reported in earlier studies that did not involve the vaccine.
• Most participants developed an immune response against the mutated IDH1 protein. Immune-cell responses to mutated IDH1 were detected in 28 of 32 treated participants and antibodies were detected in 30 of 32. Two participants who showed no measurable immune response experienced tumor progression within two years and died within three years of diagnosis.
• The timing of antibody responses appeared to be linked to better outcomes. During 47 weeks of monitoring, participants whose response was strongest at the final vaccination or afterward tended to remain free of progression and survive longer than those whose response peaked earlier.

The study also provided a glimpse of the vaccine-induced immune response inside the brain. In one participant, an enlarging area on magnetic resonance imaging (MRI) scans initially looked like tumor growth. However, tissue removed from that area instead showed substantial inflammation and contained immune cells that recognized the mutated IDH1 target. Although this evidence came from only one participant, it suggests that the vaccine could generate a targeted immune response within the brain.

Because this was a small, early-stage trial with no comparison group, it cannot prove that the vaccine is safe or that it improved survival. The survival results are also difficult to compare with earlier studies because the trial included a selected group of patients, more than half had their tumors completely removed, and tumor-grading systems have changed over time. Mutation-targeted vaccination for astrocytoma therefore remains investigational, but these data support its promise as a strategy for future cancer treatment. In episode #113, Dr. Derya Unutmaz explains how AI could enable more precise, personalized cancer treatments by identifying tumor-specific mutations and designing therapies to target them.

Live bacteria can grow inside tumors and help attack cancer, but finding strains that combine strong anti-tumor effects with acceptable safety remains a major challenge. A new study tested whether gut bacteria from amphibians and reptiles could serve as novel candidates for new cancer treatments.

Researchers isolated 45 gut bacterial strains from a Japanese tree frog, Japanese fire belly newt, and Japanese grass lizard, then selected nine for further testing after they caused no severe short-term toxicity when injected into the tail veins of mice. Each strain was then tested in mice with colon cancer cells implanted under the skin, and tumor growth was tracked for 40 days after a single injection. In a second tumor experiment, the researchers focused on Ewingella americana, isolated from the Japanese tree frog, because it was the only bacterial treatment that produced complete tumor regression without later regrowth. Mice received E. americana, anti-PD-L1 treatment (an immunotherapy that blocks a signal tumors use to suppress the immune system), liposomal doxorubicin (a chemotherapy drug carried in tiny fat-based particles), or a bacteria-free control solution. The bacterial treatment was given once at a dose of 1 billion live bacteria, while the two drug treatments were each given four times.

• In all five mice treated with E. americana, the tumors became undetectable by physical examination and did not return for at least 30 days. The same outcome occurred in one of five mice given anti-PD-L1 and none of the mice given liposomal doxorubicin or the control solution, although both standard treatments slowed tumor growth compared to control.
• Mice successfully treated with E. americana did not develop tumors after a second injection of the same cancer cells in a separate experiment. None of 10 mice previously treated with E. americana developed another tumor during the next 30 days, while 10 previously untreated mice did.
• E. americana grew rapidly inside tumors. Viable bacterial counts inside tumors rose about 3,000-fold from 3 to 24 hours.
• The administered dose showed a favorable safety profile. Researchers found no lasting abnormalities in blood tests or major organs, and bacteria were undetectable in blood by 24 hours. Short-term effects included early weight loss and a temporary inflammatory response. However, higher doses caused acute death.

To investigate how the treatment worked, researchers tested E. americana in lab-grown clusters of colon cancer cells and examined tumors from treated mice. The bacterium directly disrupted the cell clusters and killed cancer cells. Tumors of treated mice contained more immune cells, stronger inflammatory signals, and more apoptosis, a controlled form of cell death. Since E. americana can grow with or without oxygen, the low-oxygen conditions inside tumors may have helped it multiply there, concentrating its direct effects while also triggering an immune attack. This response may also have produced lasting immune memory, helping the successfully treated mice resist a second cancer cell injection.

Because the study used a mouse model of colon cancer, it cannot show whether the treatment would be safe or effective in people. Nevertheless, the findings suggest that gut bacteria from understudied animals may offer promising starting points for developing new cancer treatments. In Aliquot #141, I explore how everyday lifestyle choices influence cancer risk.

Xanthan gum is a food additive used to thicken and stabilize many processed foods. Although it is widely used, animal research has raised questions about whether regular intake could affect gut health. A new study examined whether xanthan gum could promote inflammation and alter the intestinal barrier.

The study included 32 adult male rats divided into four groups. For 10 weeks, one group ate a control diet, while the other three ate the same diet supplemented with 462.5, 925, or 1,850 milligrams of xanthan gum per kilogram of food. After the feeding period, researchers examined tissue from the lower part of the colon under a microscope and looked for proteins tied to inflammation and intestinal barrier function. They also analyzed gut bacteria and tracked food intake, body weight, and blood markers of metabolic health.

• Microscopic examination showed more inflammation, including more immune cells in the intestinal wall, in the middle- and highest-dose groups than in the control group, while the group with the lowest dose showed no clear difference.
• Staining of thin intestinal tissue slices showed that a greater proportion of cells contained TNF-α, a protein involved in inflammatory responses, at all three xanthan gum doses. Claudin-2, which forms channels between intestinal cells and can make the intestinal lining more permeable, was also found in more cells and across a wider area of the tissue in rats given xanthan gum.
• A separate test measuring total protein levels found higher IL-1β, another protein involved in inflammatory responses, only at the middle dose, while Claudin-2 and ZO-1, the latter of which helps organize the seals between intestinal cells, rose only at the lowest dose.
• Xanthan gum caused only a small change in gut bacteria. The variety of bacteria and how much of each common type was present remained similar between the diet groups.
• Body weight and blood markers of metabolic health did not clearly differ. The groups had similar food intake, weight gain, and body fat. Blood sugar and measured blood fats, including triglycerides and cholesterol, were also similar.

Xanthan gum may activate immune cells in the wall of the colon. Once activated, these cells can release proteins that attract additional immune cells into the tissue. As more immune cells accumulate and become activated, the tissue can become increasingly inflamed. The same signals can also affect the intestinal barrier, making it more permeable and allowing water and other dissolved substances to cross the intestinal lining more easily. Substances reaching the tissue beneath the lining could then further activate immune cells, reinforcing the inflammation. Because gut bacteria changed little overall, a broad disruption of the bacterial community is less likely to be the main explanation.

The study did not directly test whether the intestinal barrier became more permeable, and the inconsistent dose patterns make it less certain how confidently the observed changes can be attributed to xanthan gum. Because the study was conducted in rats, it also remains unclear whether the same effects occur in people. Confirmation in human studies would strengthen the case for greater caution around frequent intake of xanthan gum and the ultra-processed foods that often contain it. In Aliquot #111, I explain why ultra-processed foods and their additives are harmful.