Recombinant BCGs for tuberculosis and bladder cancer.

Area of Science:

• Immunology
• Vaccinology
• Oncology

Background:

• Bacillus Calmette-Guérin (BCG) is a widely used live attenuated vaccine for tuberculosis (TB), with a strong safety record and effectiveness in reducing childhood TB mortality.
• Despite its historical success, BCG's efficacy against pulmonary TB in adults is limited, and multi-drug resistant TB remains a global health challenge.
• Intravesical BCG is a standard immunotherapy for non-muscle invasive bladder cancer (NMIBC), but treatment resistance and recurrence affect a significant portion of patients.

Purpose of the Study:

• To review the development of second-generation, genetically modified BCG candidates.
• To explore their potential as improved vaccines against tuberculosis (TB).
• To evaluate their application as anti-tumor adjuvant therapy for non-muscle invasive bladder cancer (NMIBC).

Main Methods:

• Review of recent pre-clinical and clinical studies on genetically modified BCG.
• Analysis of engineered BCG strains designed for enhanced immunogenicity.
• Examination of BCG modifications for improved anti-TB and anti-tumor responses.

Main Results:

• Genetically modified BCG and alternative administration routes or revaccination strategies show potential for enhanced protection against TB.
• Engineered BCG candidates expressing specific molecules demonstrate promise for stronger anti-TB immunity and potent anti-tumor effects in NMIBC.
• These modified BCG vaccines are advancing in pre-clinical and clinical settings.

Conclusions:

• Genetically modified BCG represents a promising avenue for developing next-generation TB vaccines.
• These modified BCG strains also hold potential as novel intravesical therapies for NMIBC, addressing a significant unmet clinical need.
• BCG is poised for a resurgence through genetic modification for diverse therapeutic applications.