Mobilan, a recombinant non-replicating adenovirus vector expressing Salmonella flagellin, is currently in a phase Ib clinical trial for prostate cancer. Overall, bacterial flagellin treatments are generally safe, well-tolerated, and associated with minimal side effects, making them a promising option for managing infectious diseases and cancers.

P1, N=60, Recruiting, Institut National de la Santé Et de la Recherche Médicale, France | Not yet recruiting --> Recruiting

P1, N=60, Not yet recruiting, Institut National de la Santé Et de la Recherche Médicale, France | Initiation date: Jan 2025 --> Apr 2025

P1, N=60, Not yet recruiting, Institut National de la Santé Et de la Recherche Médicale, France

As a result, the TLR5 agonist augmented the anti-tumor efficacy of anti-PD-1, suggesting its potential in modulating the tumor microenvironment to enhance the anti-tumor response. Our findings point toward the possibility of optimizing immune checkpoint inhibitor therapy using TLR5 agonists.

Further study is needed to optimize these tactics and fill knowledge gaps. Also, the effective components of herbal, synthetic drugs, etc., should be isolated and tested up to clinical levels, paving the way for successful radioprotection and radiomitigation strategies in the male reproductive system.

While the TLR4/5 agonists contributed in the elicitation of the Th2-polarized immune responses, combination with TLR7 agonist changed the polarization to the balanced Th1/Th2 immune responses. Indeed, RP + TLR7 agonist/alum adjuvants induced the strongest immune responses that could efficiently neutralize the HPV pseudoviruses, and thus might be a promising formulation for an inexpensive and cross-reactive HPV vaccine.

CBLB502-induced enhancement of ICT was also observed in poorly immunogenic B16-F10 melanoma tumors. Combination immune checkpoint therapy plus TLR5 agonists may offer a new therapeutic strategy to treat ICT-refractory solid tumors.

These findings can facilitate the rational design of selected peptides as an agonist of TLR5, which have antitumor activity, suppress colorectal cancer tumors, and can be used as promising candidates and novel agonists of TLR5.

We also find that FnIII-1c is not recognized by MDA-MB-468 cells but is recognized by MDA-MB-231 cells, suggesting a cell type rather than ligand specific utilization of TLRs. As IL-8 plays a major role in the progression of TNBC, these studies suggest that tumor-induced structural changes in the fibronectin matrix promote an inflammatory microenvironment conducive to metastatic progression.

Indeed, we showed that exogenous activation of TLR5 signalling by recombinant Flagellin and exogenous expression of TLR5 both enhanced the therapeutic efficacy of flagellum-deficient Salmonella against melanoma. Our study highlighted the therapeutic value of the interaction between Salmonella and the host immune response through Flagellin/TLR5 signalling pathway during Salmonella-mediated cancer therapy, thereby suggesting the potential application of TLR5 agonists in the cancer immune therapy.

The FDA has now approved chemo-immunotherapy (CTx-I) regimens (αPD-L1/nab-Paclitaxel, αPD-1/CTx) as standard-of-care for early-stage, locally advanced, and metastatic TNBC. Importantly, systemically administered entolimod was shown to be safe in Phase I clinical trials cumulatively involving nearly 200 subjects in both healthy volunteers and advanced cancer patients. Thus, this work will aid in formulating a more effective CTx-I treatment regimen with potentially important clinical implications for patients with locally advanced or metastatic TNBC.