Bifidobacterium breve as a delivery vector of IL-24 gene therapy for head and neck squamous cell carcinoma in vivo

Abstract

Beneficial bacteria are becoming ever more popular gene delivery method for hypoxia-tumor targeting in vivo. In this study we investigated the therapeutic effect of new recombinant Bifidobacterium breve strain expressing interleukin (IL)-24 gene (B. breve-IL24) on head and neck tumor xenograft in mice. Briefly, B. breve transformants were obtained through electro-transformation. Bacteria-tumor-targeting ability were analyzed in vivo over different time points (1, 3 and 7 days post-bacteria injection). Furthermore, the therapeutic effect of bacteria on tumor cells in vivo were analyzed as follows: 30 Balb/c nude mice bearing subcutaneous tumor were randomly divided in three groups (Drug group, green fluorescent protein (GFP) group and Saline group). The therapy lasted for 2 weeks and included B. breve-IL24 administration via tail vein for Drug group, B. breve-GFP for GFP group and phosphate buffered saline for Saline group. The tumor growth was monitored using standard caliper technique, while the apoptosis induction in vivo was analyzed by Real-time Positron Emission Tomography/Computed Tomography (PET/CT) imaging ([18F]-ML-10 tracer). At the end of the experiment, tumor tissues were collected and analyzed by western blotting. Briefly, our results suggested that our new recombinant bacterium has the capability of targeting tumor tissue in vivo. As for the therapeutic effect, our new strain has revealed to be a promising therapeutic approach against tumor growth in vivo. Briefly, higher tumor growth inhibition and higher tumor cell apoptosis induction were observed in Drug group compared with the GFP and Saline groups. To conclude, a new recombinant strain B. breve-IL24 offers a novel, safe and clinically acceptable therapeutic approach for tumor therapy in vivo.

Exopolysaccharide, Isolated From a Novel Strain Bifidobacterium breve lw01 Possess an Anticancer Effect on Head and Neck Cancer – Genetic and Biochemical Evidences

“…In our previous study, we already verified that the strain B. breve possess an anti-tumor effect on HNSCC tumor-bearing model (Wang et al, 2017). Yet, the exact mechanism was not fully explored.…”

“…Bifidobacterium , which is one of the dominant early colonization bacteria in human intestinal tract, was proven to regulate immune development (Arboleya et al, 2012), immune modulation (Fanning et al, 2012), and to possess an anti-inflammation (Strisciuglio et al, 2015) and anticancer (Wang et al, 2017) activity. The immune response is stain-specific (Lopez et al, 2010) and one of the mechanisms driving the immune functions is regulated by bifido-EPS.…”

Clinical Significance of the Interleukin 24 mRNA Level in Head and Neck Squamous Cell Carcinoma and Its Subgroups: An In Silico Investigation

“…Adenovirus-mediated IL24 mRNA therapy could enhance the in vivo and in vitro antitumor effects of radiotherapy for NPC [ 20 , 21 ]. A study of Bifidobacterium as a carrier of the IL24 mRNA to treat HNSCC in mice showed that the recombinant strain Bifidobacterium breve -IL24 had a stronger ability to inhibit tumor growth and induce tumor cell apoptosis [ 19 ]. Although there is no suitable way to conduct clinical trials of the IL24 mRNA as a targeted therapy for HNSCC and its subgroups, the current studies suggest that the IL24 mRNA could be a potential treatment.…”

“…Recent evidence indicates that the IL24 mRNA is an underlying candidate for gene treatment of cancer through boosting apoptosis in many types of cancer cells [ 14 – 17 ]. IL24 has been reported to play vital roles in the inhibition of tumor growth and induction of tumor cell apoptosis in HNSCC cells [ 18 , 19 ]. Adenovirus-mediated IL24 mRNA therapy could also enhance the in vivo and in vitro antitumor effects of radiotherapy for NPC [ 20 , 21 ].…”

Bifidobacterium-mediated high-intensity focused ultrasound for solid tumor therapy: comparison of two nanoparticle delivery methods

“…Most studies of bacterial targeting of tumors involved direct cross-linking of the bacteria to the delivery substance or recombination of genes and bacteria as an arch on a 'bacterial robot' to target the tumor [21][22][23]. However, effective delivery of nanomedicines to tumor cells is difficult because of the complex tumor microenvironments, resulting in poor and uneven perfusion, poor vascular permeability, and a high density of stromal cells, as well as increased interstitial pressure [24].…”