TB vax primer augments BCG-induced immune response in bladder cancer patients

Initial results of the phase I RUTIVAC-1 study show the potential of two doses of a tuberculosis (TB) vaccine given after surgery but before standard BCG* treatment to boost immunity and reduce the odds of recurrence in patients with non-muscle-invasive bladder cancer (NMIBC).

Despite standard treatment with TURBT** and iBCG***, up to 50 percent of NMIBC patients still experience recurrence or progression. “Thus, novel combination therapies are needed to improve BCG efficacy,” the investigators noted.

The team sought to evaluate the potential of a heterologous prime-boost strategy using a non-live vaccine comprising Mycobacterium tuberculosis cell wall fragments as a primer to enhance the immune response induced by iBCG. Forty patients with high-grade, BCG-naïve NMIBC (median age 70 years, 90 percent men) treated with TURBT were randomized 1:1 to receive two SC doses (25 μg) of the vaccine or placebo 10 days apart, followed by standard iBCG.

In the vaccine arm, there was a modest but significant reduction in circulating CD8+ T cells (p=0.04) and a significant increase in CD4+CD27+ T-cell frequency (p=0.03). There were no significant changes in the placebo arm.

Moreover, there were no significant changes in CD4+ or CD8+ T cells or increase in CD4+CD25+ in the vaccine arm. In the placebo arm, iBCG induced significant increases in circulating CD4+ T cells (p=0.007) and activated upregulated CD4+CD25+ T cells (p=0.0028), with a concurrent reduction in CD8+ T cells (p=0.006).

“Notably, [the vaccine] prevented the increase in regulatory cells (CD4+CD25+CD27+), resulting in a significant difference in the presence of these suppressive cells between arms,” said study co-investigator Dr Roberto Hugo Martinez Rodriguez from the Hospital Universitario Rio Hortega, Valladolid, Spain, who presented the findings at EAU 2025.

“When evaluating the immunological behaviour during iBCG treatment, we appreciated a more heterogeneous, stable, sustained, and broad response in the [vaccine arm],” Rodriguez added.

Clinical efficacy, safety

At 5 years, the vaccine arm had higher rates of cancer-specific-free survival (100 percent vs 83.3 percent; p=0.067), event-free survival (89.5 percent vs 50 percent; hazard ratio, 0.2; p=0.024), and progression-free survival (PFS; 100 percent vs 72.2 percent; p=0.015). To further contextualize the PFS data, all evaluable vaccine recipients (n=19) were tumour-free 5 years later, as opposed to 13 out of 18 in the control arm.

In the EAU press release, principal investigator Dr Cecilia Cabrera from IrsiCaixa and Germans Trias i Pujol Research Institute, Barcelona, Spain, said, “We expected that the vaccine would improve immune response … but we did not know what effect this might have on cancer progression over 5 years. [We were] very surprised to see such a vast improvement in cancer progression even with such a small group of patients.”

“[Although] this was a small pilot study … we have been encouraged by the reduction in disease recurrence and progression [in the vaccine arm],” noted Cabrera. “With such high rates of recurrence in bladder cancer, finding new ways to prevent this is very important.”

The vaccine was also well tolerated, with only mild injection site reactions reported and no systemic adverse effects.

A promising therapeutic strategy

“[Administering the vaccine] prior to iBCG in NMIBC patients is safe and significantly enhances the BCG-induced immune response by promoting a more diverse, polyfunctional, and balanced effector/regulatory immune response,” said Rodriguez. “The observed immunomodulation may be associated with the improved survival outcomes in vaccinated patients.”

“This phase I study demonstrated the safety and immunogenicity of the vaccine in NMIBC patients receiving iBCG, suggesting that [this novel approach] represents a promising therapeutic strategy for improving clinical outcomes in NMIBC management,” he added.

“This is a well-conducted pilot study and shows promising results. With just two injections over and above standard treatment, the burden on patients is very small,” commented EAU Scientific Congress Office member Professor Joost Boormans from the Erasmus University Medical Centre, Rotterdam, the Netherlands. “I look forward to seeing whether further studies in larger cohorts continue to demonstrate the benefits to patients and improve their outcomes.”

The vaccine is being developed as a therapeutic vaccine against TB and an immunotherapeutic agent for bladder cancer.