What question did this study set out to answer?

To evaluate the efficacy and safety of rBCG-h12, an engineered BCG strain, against bladder and pancreatic cancers.

June 3, 2026Open Access

Preclinical evaluation of rBCG-h12: an engineered Bacillus Calmette-Guérin with an enhanced activity against bladder and pancreatic cancers

Key Points

To evaluate the efficacy and safety of rBCG-h12, an engineered BCG strain, against bladder and pancreatic cancers.
Safety assessed in NOD/SCID and C57BL/6 mice over four weekly instillations
Antitumor efficacy tested using orthotopic NMIBC transplant models and K-RasG12D mouse models
Immune microenvironment changes measured through detection of macrophage and T cell markers.
rBCG-h12 significantly suppressed bladder tumor growth compared to conventional BCG, prolonging survival and mitigating cachexia.
No mortality, weight loss, hematuria, or organ pathology observed in treated mice.
Single intramuscular injection of rBCG-h12 reduced desmoplasia and extended survival in pancreatic cancer models without adverse pathological effects.

Abstract

Intravesical Bacillus Calmette-Guérin (BCG) therapy has been the standard treatment for preventing recurrence of non-muscle-invasive bladder cancer (NMIBC) for over four decades. Although maintenance BCG therapy improves recurrence-free survival in intermediate- and high-risk NMIBC patients, its long treatment duration, toxicity, and limited efficacy - particularly in carcinoma in situ -necessitate the development of improved therapeutic alternatives. rBCG-h12 is a recombinant BCG strain engineered to enhance immunogenicity. This study evaluated its ability to augment macrophage activation and antitumor responses. The safety of intravesical rBCG-h12 was evaluated in NOD/SCID and C57BL/6 mice through four weekly instillations. Body weight, survival, urine hematuria, and organ histopathology were monitored. Antitumor efficacy was tested using an orthotopic NMIBC transplant model. Immune microenvironment changes were analyzed by detecting macrophage and T cell markers. The systemic antitumor potential of rBCG-h12 was further evaluated via intramuscular injection in pancreatic cancer transplant and K-RasG12D mouse models. Intravesical rBCG-h12 was well tolerated, with no observed mortality, weight loss, hematuria, or organ pathology. Compared with conventional BCG, rBCG-h12 more effectively suppressed bladder tumor growth, prolonged survival, and mitigated cachexia. Mechanistically, rBCG-h12 decreased CD206+ M2-macrophages while increasing CD4+TNF-α+ effector T cells and CD8+TNF-α+ cytotoxic T cells. In pancreatic cancer models, a single intramuscular injection of rBCG-h12 markedly reduced desmoplasia, suppressed tumor growth, and extended survival without inducing pathological lesion or granuloma formation in liver, lungs, and spleen. rBCG-h12 exhibited superior antitumor efficacy and safety compared with BCG. By suppressing M2-macrophages and promoting Th1 immune activation, rBCG-h12 shows promise as a next-generation BCG-based immunotherapy for both bladder and pancreatic cancers.

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