A Novel Heterologous Prime-boost Strategy Using RUTI Vaccine to Improve the Bacillus Calmette-Guérin Response in...

Area of Science:

• Immunology
• Oncology
• Vaccinology

Background:

• Intravesical bacillus Calmette-Guérin (BCG) is standard for high-risk non-muscle-invasive bladder cancer (NMIBC).
• Recurrence and progression remain significant challenges despite BCG treatment.
• Novel strategies are needed to improve outcomes for NMIBC patients.

Purpose of the Study:

• To evaluate the immunogenicity, safety, and preliminary efficacy of RUTI, a nonlive Mycobacterium tuberculosis vaccine.
• To assess RUTI as a systemic primer before intravesical BCG in high-risk NMIBC patients.
• To explore a heterologous prime-boost vaccination strategy.

Main Methods:

• Phase 1, randomized, double-blind, placebo-controlled RUTIVAC-1 trial (NCT03191578).
• 40 high-risk NMIBC patients received two subcutaneous doses of RUTI (25 μg) or placebo.
• Immunogenicity assessed by flow cytometry; clinical follow-up up to 5 years.

Main Results:

• RUTI induced systemic vaccine-specific T-cell responses (CD4+ and CD8+).
• RUTI vaccination prevented regulatory T-cell expansion seen in placebo group.
• RUTI was safe, well-tolerated, with mild injection-site reactions.
• Exploratory analysis suggested a trend towards reduced recurrence, progression, and improved 5-year progression-free survival.

Conclusions:

• RUTI is safe and immunogenic as a prime for BCG in NMIBC.
• The vaccine elicits a robust and polyfunctional immune response.
• Further investigation in larger trials is warranted to confirm clinical benefit.