Vesimune (imiquimod intravesical)

MTT (thiazolyl blue tetrazolium bromide) assays were conducted to determine non-cytotoxic concentrations of the immunomodulatory agents: 25 µM IMQ (imiquimod), 10 µg PPG (peptidoglycan), 1 mg LPS (lipopolysaccharide), and two BCG doses (200 µg/mL and 800 µg/mL). These findings suggest distinct immunomodulatory responses between cancer subtypes, emphasizing the need for tailored approaches targeting the PD-1/PD-L1 axis. Further studies should explore the molecular mechanisms underlying these differential effects and assess the potential for combinatorial immunotherapeutic strategies in cancer.

P1, N=10, Suspended, M.D. Anderson Cancer Center | Trial completion date: Aug 2025 --> Aug 2026 | Trial primary completion date: Aug 2025 --> Aug 2026

P1, N=51, Active, not recruiting, UroGen Pharma Ltd. | Recruiting --> Active, not recruiting

We found elevated levels of mitochondrial DNA in patients with psoriasis, along with high expression of AIM2 in both the human psoriatic epidermis and a mouse model of psoriasis induced by topical imiquimod (IMQ) application. Finally, the genetic absence of inflammasome components downstream AIM2, ASC, and caspase-1 alleviated IMQ-induced skin inflammation. Collectively, our data show that AIM2 is involved in developing psoriasis through its canonical activation.

P1, N=10, Suspended, M.D. Anderson Cancer Center | Trial completion date: Aug 2024 --> Aug 2025 | Trial primary completion date: Aug 2024 --> Aug 2025

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.