P2, N=85, Recruiting, Baylor College of Medicine

P1, N=15, Active, not recruiting, Medical University of South Carolina | Trial completion date: Sep 2024 --> Dec 2024

P=N/A, N=6, Terminated, University of California, Davis | N=110 --> 6 | Active, not recruiting --> Terminated; PI failed to submit the study for continuing review to IRB, failed to respond.

P1, N=146, Completed, Jiangsu HengRui Medicine Co., Ltd. | Not yet recruiting --> Completed | N=104 --> 146

Nrf2 and GPX4 might be the two major targets of SHK in psoriatic skin lesion. Our study highly lighted the basic biological mechanism of SHK on ferroptosis regulation.

This work suggests that the highly lipophilic prodrug approach can efficiently deliver IMQ to intestinal lymphatics. In addition, this study demonstrates the feasibility of an amide prodrug approach for intestinal lymphatic targeting.

Oral propranolol is a mainstay of treatment for IH and is well-tolerated, though propranolol-refractory IH and other drug-related adverse events are documented and can limit its usage. From this preliminary analysis, we discerned that hemangioma tissues can be grown in tissue culture and used for drug treatment studies. We also conclude acute and chronic modulation of cell cycle, angiogenesis factors, and immunostimulatory conditions may be associated with imiquimod mechanisms of action in hemangioma involution.

P1/2, N=188, Active, not recruiting, Ascendis Pharma Oncology Division A/S | Recruiting --> Active, not recruiting

BML-111 modulates the p38/MAPK signaling pathway and Th1/Th2/Th17 cytokine response, and alleviates psoriasis-like dermatitis in mice.

A mouse model for psoriasis combined with SDs was established by smearing 62.5 mg of 5% imiquimod (IMQ) cream for seven consecutive days, along with a daily injection of p-chlorophenyl alanine (PCPA) solution at a dosage of 300 mg/kg at days 6-7...XYAS may treat psoriasis complicated by SDs through two main mechanisms: (1) Improving melatonin-RORα axis in the skin can lead to an increase in mnSOD and a reduction in Cyt-C levels, which provide protection against oxidative stress, mitochondrial damage, and psoriatic inflammation. (2) Reducing IL-6, IL-17A, and TNF-α production to suppress IL-23/Th17 pro-inflammatory signaling axis and epidermal hyperplasia in psoriasis.

Local therapies can be considered in superficial and low-risk nodular BCCs, with imiquimod frequently used for its antitumor and immunoregulatory properties...Interferons and Interleukin-2 were evaluated in a small number of studies with different results. Systemic immunotherapies with programmed death-ligand 1 (PD-L1) inhibitors showed inconsistent results in patients with advanced BCCs, being effective in some patients that progressed on or were intolerant to hedgehog pathway inhibitors (HHI).

In the imiquimod (IMQ) -induced mouse inflammatory model, the therapeutic effect of GFRS on the pathogenesis of psoriasis-like dermatitis was studied...GFRS restored IMQ-induced spleen size and reduced the secretion and expression of TNF-α, IL-6, Interferon-γ (IFN-γ) and IL-17 A in serum. In summary, our results demonstrate that GFRS alleviates IMQ-induced dermatitis symptoms, effectively reduces the secretion of inflammatory factors, and inhibits IL-17 A expression.

An 87-year-old female presented with a recurrent vulvar lesion refractory to topical imiquimod and treated with multiple wide local excisions (WLE)...AAEMPD, a rare variant of EMPD, shares similar prognosis and behavior with the classic Paget disease. Recognition and accurate diagnosis of this subtype is crucial for optimal patient management, given distinct treatment strategies compared with other entities in the differential diagnosis.

P1/2, N=473, Recruiting, Ascendis Pharma Oncology Division A/S | Trial completion date: Aug 2027 --> Aug 2029 | Trial primary completion date: May 2026 --> Aug 2027

A psoriasis-like skin inflammation mouse model was induced by imiquimod (IMQ) and treated with BBR and a p38 activator anisomycin...BBR repressed NLRP3 inflammasome activation and pyroptosis by inhibiting the p38 MAPK/NF-κB pathway. Collectively, BBR suppressed keratinocyte NLRP3/GSDMD pathway pyroptosis by suppressing the p38 MAPK/NF-κB pathway, thereby affecting psoriasis skin inflammation.

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.

Adding a STAT-3 inhibitor yielded similar effects to IMQ, altering cell proliferation, migration and apoptosis. Overall, IMQ appears to inhibit U87 cell proliferation and migration, inducing programmed cell death through STAT-3 modulation.

Our results suggest that elevated SKP2 can empower keratinocytes proliferation and psoriasis-like epidermis hyperplasia via downregulation of P27 Kip1. Therefore, targeting SKP2-P27 Kip1 axis might be a promising therapeutic strategy for the treatment of psoriasis in future.

P1, N=7, Active, not recruiting, Mayo Clinic | Trial completion date: Dec 2024 --> Dec 2025

Mcl-1 overexpression ameliorates IMQ-induced ROS generation and mitochondrial fragmentation, thereby increasing mitochondrial stability and ultimately attenuating IMQ-induced cell death. Investigating the roles of Mcl-1 in mitochondria is a potential strategy for cancer therapy development.

In addition, an immune adjuvant of imiquimod (R837) is incorporated...Specifically, QUE inhibits the activation state of hepatic stellate cells and reduces highly expressed programmed death receptor ligand 1 (PD-L1) on tumor cells, meanwhile R837 exposes calreticulin on tumor cell surface as an "eat me" signal and leads to a large number of DCs maturing for enhanced antigen presentation. Consequently, the cooperative immune regulation results in a remodeled TME with high infiltration of cytotoxic T lymphocytes for enhanced HCC immunotherapy, which demonstrates an effective immunotherapy paradigm for dense ECM characterized solid tumors with high PD-L1 expression.

We showed that TLR7 activation by imiquimod in peripheral blood monocyte-derived CD11c+ DCs triggered mROS production, leading to enhanced IL-12 secretion and subsequent NK cell activation, as evidenced by increased IFN-γ production and tumor cell cytotoxicity. Notably, mROS neutralization abrogates NK cell-mediated tumor cell lysis, and TLR7-mediated DC activation of NK cells occurs independently of MyD88, suggesting involvement of the noncanonical NF-κB pathway. Our findings provide a rationale for targeting the TLR7/mROS/IL-12 axis to enhance the efficacy of DC-based cancer immunotherapy.

CarboCell can be injected through standard thin-needle technologies and has inherent imaging contrast which secure accurate intratumoral positioning. In particular, here we report the therapeutic performance for a dual-drug CarboCell providing sustained release of a Toll-like receptor 7/8 agonist and a transforming growth factor-β inhibitor in preclinical tumor models in female mice.

Representative agonists from this series were successfully able to induce the production of various proinflammatory cytokines and chemokines from human peripheral blood mononuclear cells. Anti-HER2-25 and anti-HER2-26 ADCs made from this class of payloads demonstrated mechanism-based activation of TLR7/8 in a THP1/N87 coculture system.

Assisted by imiquimod, substantial CTL infiltration occurs, accompanied by pro-inflammatory factor release (TNF-α, IL-6), transforming M2 macrophages into the M1 phenotype. Ultimately, the proposed strategy combines PD-L1/PD-1 blockade, imiquimod and mild thermal treatment to synergistically enhance tumor immunogenicity, remodel the TME, and restrain hepatic carcinoma, making strides in ICB synergistic immune-thermal therapy.

P1/2, N=40, Recruiting, Shanghai Zhimeng Biopharma, Inc. | Not yet recruiting --> Recruiting | Trial completion date: Mar 2024 --> Dec 2025 | Trial primary completion date: Mar 2024 --> Dec 2024

P2, N=90, Recruiting, Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

P1/2, N=175, Active, not recruiting, Bolt Biotherapeutics, Inc. | N=390 --> 175 | Trial completion date: Oct 2026 --> Jan 2026

P2, N=11, Active, not recruiting, Bolt Biotherapeutics, Inc. | N=66 --> 11

Taken together, these data demonstrate that RT combined with a nanoformulated immunostimulant diminished the immunosuppressive TME resulting in tumor regression. These findings set the stage for clinical studies of this approach.

phenformin ameliorates the psoriasis-like inflammatory response by inhibiting c-Myc expression in keratinocytes, suggesting its potential as a topical drug for the treatment of psoriasis.

NPS in combination with the adjuvant and TLR agonist, resiquimod (RES), was the optimal treatment regimen for both eliminating a primary Pan02 tumor as well as inhibiting growth of a Pan02 cell rechallenge tumor...NPS plus RES was the most effective at both eliminating a primary tumor and inhibiting a rechallenge tumor. NPS treatment followed by injection of aOX40 was the most effective at inhibiting the growth of an untreated abscopal tumor.

P2, N=48, Recruiting, National Institute of Allergy and Infectious Diseases (NIAID) | Trial completion date: Jul 2025 --> May 2027 | Trial primary completion date: Jan 2025 --> Nov 2026

Additionally, they decreased the migration (from ∼24 % to ∼8 %; p < 0.0001) and invasion (to 11 %; p = 0.0047) capacities of the cancer cells. In summary, the produced liposomes represent a promising approach to enhance the anticancer potential of IQ in head and neck cancer, particularly in tongue cancer.

P2, N=103, Completed, Gilead Sciences | Active, not recruiting --> Completed

Imiqualines are analogues of the immunomodulatory drug imiquimod...In summary, we showed that EAPB02303 potently reduced the activity of IIS and Ras-MAPK signaling in C. elegans. Our results revealed the mechanism of action of EAPB02303 against human cancers associated with hyperactivated IIS pathway and oncogenic Ras mutations.

P1, N=7, Active, not recruiting, Mayo Clinic | Trial completion date: Jun 2024 --> Dec 2024

The study showed that LIT inhibited the growth of both primary and abscopal melanoma by activating systemic antitumor immune responses and reversing the immunosuppressive tumor microenvironment, making LIT a potential method for advanced melanoma treatment.

Additionally, cancer immunotherapy using immune drugs, such as imiquimod (R837), has shown promise in activating T cells to kill tumor cells...Our results indicate that these six key genes regulate immune cell recruitment to increase T-cell cytotoxicity and kill tumors. Targeting these key genes can enhance immunotherapy and improve the breast cancer prognosis.

Our results indicate that altered MDAC properties in psoriatic condition sustains pathological inflammation and RORγt and NFAT1 as promising intervention target for psoriasis management.

Toll-like receptor 7 (TLR7) agonist imiquimod (IMQ) and bispecific antibody (BsAb) blinatumomab were loaded onto PDA-CaCO3 nanoparticles (NPs). PICB had a strong inhibitory effect on tumor growth in 4T1 tumor-bearing mice, and has no toxicity to other organs. Therefore, the multifunctional drug delivery nanosystem constructed in this study could effectively exert the properties of various components in vivo, fully demonstrate the synergistic effect between immunotherapy and photothermal therapy, thus significantly improving the tumor therapeutic efficacy, and has a promising clinical application.

P1/2, N=75, Recruiting, SURGE Therapeutics | Trial completion date: Sep 2024 --> Dec 2025 | Trial primary completion date: Jun 2024 --> Dec 2025