Finally, Gln was sufficient to promote IFN-γ-production in IMQ-treated T cells. Our findings indicate that Gln metabolism can be harnessed for treating KDSCs.

PCN-224@FcCaO2/Mn/dihydroartemisinin/imiquimod/PDA (PFC) was prepared by modified with dihydroartemisinin (DHA), imiquimod (R837), CaO2, ferrocene (Fc) and Mn2+ on the PCN-224 (Cu) to achieve self-replenishment of H2O2/O2 and GSH consumption...The released R837 and tumor-associated antigens from SDT/PTT can produce damage associated molecular patterns (DAMPs), which can initiate adaptive immune responses to kill cancer cells, and released again to promote the tumor immune cycle. What's more, SDT/PTT and ferroptosis combined with aPD-L1 can effectively suppress both primary and distant tumor growth.

P1, N=15, Active, not recruiting, Medical University of South Carolina | Trial completion date: Mar 2024 --> Sep 2024 | Trial primary completion date: Dec 2023 --> Jun 2023

P=N/A, N=142, Recruiting, Maastricht University Medical Center | Not yet recruiting --> Recruiting

Our study provides a novel explanation that TNF-α/caspase-3/GSDME-mediated keratinocyte pyroptosis is highly responsible for the initiation and acceleration of skin inflammation and progression of psoriasis.

P1, N=50, Active, not recruiting, Eikon Therapeutics | Trial primary completion date: Mar 2024 --> Aug 2024 | Trial completion date: Mar 2024 --> Aug 2024

P1, N=40, Active, not recruiting, Eikon Therapeutics | Trial completion date: Mar 2024 --> Jul 2024 | Trial primary completion date: Mar 2024 --> Jul 2024

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

Understanding the nuanced dynamics of immune checkpoints sheds light on IMQ mechanism of action. Further exploration is warranted to decipher the intricate mechanisms underlying IMQ treatment in the context of cervical lesions.

This study presents a combined chemoimmunotherapeutic strategy that employs a biocompatible macroporous scaffold-based cancer vaccine (S-CV) and a sialic acid (SA)-modified, doxorubicin (DOX)-loaded liposomal platform (DOX@SAL). The S-CV contains whole tumor lysates as antigens and imiquimod (R837, Toll-like receptor 7 activator)-loaded PLGA nanoparticles as immune adjuvants for cancer, which enhance dendritic cell activation and cytotoxic T cell proliferation upon localized implantation. When administered intravenously, DOX@SAL specifically targets and delivers drugs to activated neutrophils in vivo, mitigating neutrophil infiltration and suppressing postoperative inflammatory responses. In vivo and vitro experiments have demonstrated that S-CV plus DOX@SAL, a combined chemo-immunotherapeutic strategy, has a remarkable potential to inhibit postoperative local tumor recurrence and distant tumor progression, with minimal systemic toxicity, providing a new concept for postoperative treatment of tumors.

P4, N=96, Not yet recruiting, Barretos Cancer Hospital

A higher regression rate than expected was observed in the surveillance arm of this prospective trial. Future clinical trials with imiquimod targeting CIN3 patients are warranted.

In summary, these results suggested that FMN played an anti-inflammatory and anti-proliferative role in alleviating psoriasis by inhibiting IFN signaling pathway, and FMN could be used as a potential therapeutic agent.

In this investigation, a mild psoriatic phenotype was observed in mice upon topical application of IFN-α cream, and the inflammation was exacerbated when combined with imiquimod (IMQ). Immunohistochemical analyses demonstrated that IFN-α induces psoriatic inflammation in mice by stimulating phosphorylation of forkhead box O3, consistent with the involvement of this protein in cell proliferation, apoptosis, and inflammation. Our results suggested that topical IFN-α caused psoriatic inflammation and that the psoriatic inflammation was exacerbated by the combination of IFN-α and IMQ, possibly due to the dysfunction of forkhead box O3.

XCHD showed the therapeutic effect on psoriasis by regulating keratinocyte differentiation, and suppressing inflammation and angiogenesis, which provided a theoretical basis for further experiments and clinical research.

QZLX restrains the apoptosis of keratinocyte in psoriasis-like mice by downregulating the MDA-5 pathway. The restoration of the balance between cell apoptosis and proliferation in the skin may lead to considerable psoriasis relief. Our study reveals the possible molecular processes behind the effects of QZLX therapy on the skin lesions of psoriasis, and lends support to its clinical efficacy.

The combination of these three drugs altered the TME and promoted an increase in anti-tumor immune components. This may provide a promising new treatment strategy for colon cancer.

P1, N=25, Recruiting, Northwestern University | Not yet recruiting --> Recruiting

This topical regimen consisted of tazarotene cream, imiquimod cream, and 5-fluorouracil solution, applied for 30 days. This case marks the first recorded instance of successful topical medical treatment of AFX, offering an alternative for patients who may opt out of surgical intervention. Continued research to assess the broader efficacy of this approach is encouraged.

P1, N=50, Not yet recruiting, Inimmune Corporation

Ramelteon ointment (0.1%) was comparable to that of clobetasol (0.05%) ointment in alleviating a mouse model of imiquimod-induced psoriasiform inflammation; this is probably due to its potential anti-inflammatory and immunomodulatory activities. Therefore, ramelteon could be a good additive option for therapeutic management of immune-triggered inflammatory conditions such as psoriasis.

P1, N=60, Recruiting, Suzhou Zelgen Biopharmaceuticals Co.,Ltd | Not yet recruiting --> Recruiting | Initiation date: Dec 2023 --> Aug 2023

P2, N=70, Recruiting, Eikon Therapeutics | Not yet recruiting --> Recruiting

We investigated the effects of supplementing with SBM through intragastric administration or smear administration in a murine model of imiquimod-induced psoriasis...Meanwhile, the activation of endothelial cells was inhibited, accompanied by a decrease in the expression of Cxcl16. In vitro, the addition of TSG to HaCaT cells resulted in significant suppression of IL23 expression stimulated by tumor necrosis factor-alpha (TNF-α).

The protective effect of SC against psoriatic-associated inflammation reveals its potential therapeutic value for treating psoriasis.

In current study, we demonstrated that Gpr15lg (ortholog of GPR15LG) knockdown attenuated the severity of imiquimod (IMQ)-induced psoriasis-like inflammation in mice. Such an effect was achieved by down-regulating the expression of inflammatory cytokines interleukin (IL)-1α, IL-1β, tumor necrosis factor (TNF)-α and S100A7. Consistently, GPR15LG knockdown in vitro significantly downgraded the expression of inflammatory factors in the cellular model of psoriasis. These results suggested that GPR15LG could be involved in the development of psoriasis by regulating inflammation.

Mice devoid of LIGHT, or deletion of either of its receptors, lymphotoxin β receptor (LTβR) and herpesvirus entry mediator (HVEM), in keratinocytes, were protected from developing imiquimod-induced psoriatic features, including epidermal thickening and hyperplasia, and expression of PS-related genes...Moreover, in vitro, LIGHT upregulated a broad spectrum of genes in human keratinocytes that are clinical features of both PS and AD skin lesions. Our data suggest that agents blocking LIGHT activity might be useful for therapeutic intervention in PS as well as in AD.

Anti-TL1A antibody was injected into an imiquimod (IMQ)-induced murine psoriasis model...TL1A exacerbated the dermal symptoms induced by IL-23 injection in wild-type but not in γδT cell-deficient mice. These findings suggest a novel regulatory mechanism of γδT cells through TL1A and its involvement in psoriasis pathogenesis as a possible therapeutic target.

The generation of imiquimod resulted in the expression of pro-inflammatory cytokines. The re-educated M1-like macrophages feature enhanced phagocytosis of cancer cells, leading to efficient macrophage-based tumor cell killing.

P1, N=40, Active, not recruiting, Eikon Therapeutics | Trial primary completion date: Dec 2023 --> Mar 2024

P1, N=50, Active, not recruiting, Eikon Therapeutics | Trial primary completion date: Dec 2023 --> Mar 2024

P1, N=1, Active, not recruiting, Eikon Therapeutics | Trial completion date: Mar 2024 --> Mar 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

P2, N=20, Recruiting, Melanoma Institute Australia | N=10 --> 20 | Trial completion date: Dec 2023 --> Jun 2024 | Trial primary completion date: Dec 2023 --> Jun 2024

P=N/A, N=142, Not yet recruiting, Maastricht University Medical Center

P2, N=70, Not yet recruiting, Eikon Therapeutics

Additionally, we formulated a compound cocktail (CpdC), which significantly reduced psoriasis area and severity index (PASI) scores and the expressions of IL-23 and Ki67 in an imiquimod (IMQ)-induced psoriasis mouse model. Collectively, our study elucidates the primary molecular targets and active components of OYF, offering novel insights for psoriasis treatment.

Moreover, Atuveciclib interfered with the abnormal STAT3 signaling pathway through the inhibition of CDK9, which ultimately ameliorated psoriatic-like skin inflammation. These suggested that CDK9 inhibition is a potential strategy for batting psoriasis.

While NHWD-870 could inhibit IRF7 and phosphorylated-IRF7 expression in vivo and in vitro. These results indicate that NHWD-870 suppresses the maturation and activation of DCs by decreasing IRF7 proteins which finally alleviates psoriasis-like skin lesions, and NHWD-870 may be a potent therapeutic drug for psoriasis.

Here, we report a novel gene engineered exosome which is rationally designed by engineering PD1 gene and simultaneously enveloping an immune adjuvant imiquimod (PD1-Imi Exo) for boosting response of cancer immune checkpoint blockage therapy...In conclusion, the gene engineered exosome could be used for reversing T cell exhaustion in cancer immunotherapy. This study also offers a promising new strategy for enhancing PD1/PDL1 therapeutic efficacy, preventing tumor recurrence or metastasis after surgery by rebuilding the patients' immunity, thus consolidating the overall prognosis.

In this study, we reported a cancer cell membrane-coated zeolitic imidazole framework-8 (ZIF-8) encapsulating pyroptosis-inducer oxaliplatin (OXA) and immunomodulator imiquimod (R837) for chemoimmunotherapy. With the assistance of DNA methyltransferase inhibitor decitabine (DCT), upregulated Gasdermin E (GSDME) was cleaved by OXA-activated caspase-3, further inducing tumor cell pyroptosis, then localized antitumor immunity was enhanced by immune adjuvant R837, followed by triggering systemic antitumor immune responses. These results provided a proof-of-concept for the use of cell membrane-coated biomimetic nanoparticles as a promising drug carrier of combination therapy and a potential insight for pyroptosis-based melanoma chemo-immunotherapy.

While no significant alterations were observed in T cell numbers (CD8, CD4 or Treg), TAM-reprogramming in treated mice was confirmed by the relative decrease of interstitial versus alveolar macrophages, having higher CD86 expression but lower CD206 and Arg1 expression in the same cells, in treated mice. Mannose-HA-protamine-NCs loaded with poly(I:C)+R848 successfully reprogram TAMs in vivo, and reduce tumor progression and metastasis spread in mouse tumors.

We induced a mouse model with experimental psoriasiform dermatitis by Imiquimod (IMQ)...Importantly, we found that LRG1-enriched EV regulates macrophages via TGF beta Receptor 1 (TGFβR1) dependent process. Our findings indicated a novel mechanism for promoting psoriasiform dermatitis, which could be a potential therapeutic target.