Vesimune (imiquimod intravesical)

P1, N=60, Recruiting, UroGen Pharma Ltd. | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

P1, N=10, Suspended, M.D. Anderson Cancer Center | Recruiting --> Suspended

BSMCs from healthy and severe and non-severe asthmatic patients were infected with RV1B or stimulated with the PRR agonists poly(I:C) (Toll-like receptor 3 (TLR3)), imiquimod (TLR7) and poly(I:C)/LyoVec (retinoic acid-inducible gene 1 (RIG-I)/melanoma differentiation-associated protein 5 (MDA5)). RV-induced IL-33 expression was mainly regulated by TLR3 and downstream via TAK1. These signalling molecules represent potential therapeutic targets for treating asthma exacerbations.

In imiquimod-induced psoriasis-like mouse skin, topical application of the proanthocyanidin suppressed hyperplasia, decreased inflammatory cell infiltration, and down-regulated expression of the psoriasis-associated genes Il17a, Il22, S100a9, and Krt1. Red-kerneled rice proanthocyanidin inhibits 5-lipoxygenase, resulting in a decrease in leukotriene B production and psoriasis-like mouse skin inflammation. These results suggest that this proanthocyanidin may be therapeutically effective for treating leukotriene-related diseases.

To conclude, our results indicate that the widely used inflammatory drug, imiquimod, is not only a TLR7 agonist, but also harbors a novel anti-inflammatory function as a PDE inhibitor. This off-target affects the desired therapeutic inflammatory activity of imiquimod and may be accountable for adverse side effects.

IL-2 may be considered for the treatment of ITM with multiple or rapidly developing lesions where there would otherwise be significant morbidity with surgery, given pCR rates and toxicity.

We incubated normal human epidermal keratinocyte (NHEKs) or human leukemia monocytic cell line THP-1 with synthetic dsRNA, dsDNA, High Mobility Group Box 1 (HMGB1), or Toll-like receptor 7 agonist imiquimod, and examined cytokine production. Since LL-37 is a biphasic and cationic peptide, these data suggested that LL-37 selectively interacts with scavenger receptors and intermediates between DAMPs and scavenger receptors to facilitate DAMPs signaling in epithelial cells and mononuclear cells. These data imply us that the blockage of the interaction among LL-37, DAMPs and scavenger receptors can be novel therapeutic targets of innate type skin inflammation.

Given the young age of our patient and linear distribution of BCCs on non-sun exposed skin, our findings suggest segmental mosaicism. The patient was treated with topical 5% imiquimod with histologically confirmed clearance of BCCs in 2 months.

In solid organ transplant patients who lack surgical options and are not eligible for treatment with a BRAF inhibitor, and for whom treatment with checkpoint inhibitors present risk of organ rejection, T-VEC either alone or in combination with topical imiquimod should be considered for patients with locally advanced disease. This combination should be a consideration, with close observation, in patients with a history of organ transplantation and immunosuppression.

Furthermore, TLR7-induced monocyte-derived IL-1β is critical for promoting the astrocyte response. Overall, this study provides a potential mechanism for TLR7-mediated neuroinflammation.

Herein, we have reported a photothermal-immunotherapy of melanoma using pegylated black phosphorus nanosheets (BP-PEG NSs) and imiquimod (R837) as the photothermal conversion agent and the immunoadjuvant, respectively. In vivo antitumor studies in B16 tumor-bearing mice demonstrated that photoimmunotherapy showed the best tumor inhibition effects. Our study suggested that BP-PEG NS-based PTT primed with an immunoadjuvant can be used for synergistic photoimmunotherapy of melanomas.

This randomized prospective study shows that imiquimod reduces the LM area (-50%) after one month of treatment. Reducing the surface of LM with imiquimod is not associated with a higher risk of intralesional excision (marge 5mm), with a significant esthetic result (less excised surface). Research Funding: French Hospital Clinical Research Program in Cancer

Their effector cell function could be restored by additional peritumoral treatment with the TLR7 agonist imiquimod, a clinically approved agent for nonmelanoma skin cancer. Indeed, resistance to BRAFi therapy was delayed and accompanied by high numbers of activated T and NK cells in tumors. Thus, combining BRAFi with an immune stimulating agent such as a TLR ligand could be a promising alternative approach for the treatment of melanoma.