Immunotherapeutic effects of de novo benzimidazole derivative and prebiotic bacterial levan against triple-negative breast tumors by harnessing the immune landscape to intercept the oncogenic transcriptome

Abstract

The current study aimed to investigate the therapeutic potential of a novel benzimidazole derivative (BMPE) and a prebiotic bacterial levan (LevAE) against triple-negative breast cancer (TNBC) in a 4T1-cell syngeneic mouse model and to elucidate the immunological and molecular mechanisms underlying the phenotypic changes observed in treated tumors. The metastatic TNBC model was successfully established by subcutaneous inoculation of 100 μL of 4T1 cell suspension (~6000 cells) in the mammary glands of adult female BALB/c mice after brief immunosuppression one day before cell implantation. The therapeutic efficacy of BMPE and LevAE was biochemically, immunologically, and immunohistochemically evaluated. Both compounds exhibited significant antitumor and antimetastatic effects through modulating the tumoral and systemic immune milieus and restoring the TME redox status, which ultimately suppressed the oncogenic transcriptome in the treated breast tumors. Compared to the reference drug (Doxorubicin), BMPE treatment resulted in nearly complete remission within 21 days of treatment, whereas LevAE was less convenient but produced a significant curative outcome. In light of these findings, BMPE and LevAE provide new paradigms for cancer immunotherapy.