Vesimune (imiquimod intravesical)

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

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.