Topical imiquimod and intralesional interleukin-2 increase activated lymphocytes and restore the Th1/Th2 balance in patients with metastatic melanoma

Green, D.S.; Dalgleish, A. G.; Belonwu, N.; Fischer, Martina; Bodman‐Smith, Mark

doi:10.1111/j.1365-2133.2008.08709.x

Cited by 46 publications

(38 citation statements)

References 36 publications

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“…Although antiangiogenesis and apoptosis induction have also been suggested as the mechanism of the antitumor action of imiquimod, its major mechanism is believed to be mediated via activation of dendritic cells (DCs) and promoting the generation of Ag-specific CTLs (7)(8)(9). Imiquimod has been shown to be a potent adjuvant for cancer vaccine (3,8,10) and to other local treatment, such as cryosurgery (11) and intralesional IL-2 (12). Although imiquimod has demonstrated efficacy in superficial cancers, its activity in invasive cancer is less well studied.…”

mentioning

confidence: 99%

Treatment Failure of a TLR-7 Agonist Occurs Due to Self-Regulation of Acute Inflammation and Can Be Overcome by IL-10 Blockade

Lu¹,

Wagner²,

Gad³

et al. 2010

The Journal of Immunology

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mentioning

confidence: 99%

Treatment Failure of a TLR-7 Agonist Occurs Due to Self-Regulation of Acute Inflammation and Can Be Overcome by IL-10 Blockade

Lu¹,

Wagner²,

Gad³

et al. 2010

The Journal of Immunology

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“…Likewise, the patient presented here was treated in our clinic with a combination of skin-directed, intralesional, and systemic immunotherapies commonly used for cutaneous metastases of malignant melanoma 25,26 . Our case highlights a common problem in patients with mcc metastasis: most are old and have significant comorbidities that limit the tolerability-and therefore the success-of aggressive chemotherapy and immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

Immunotherapy with Imiquimod and Interferon Alfa for Metastasized Merkel Cell Carcinoma

et al. 2016

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Merkel cell carcinoma (mcc) is a highly aggressive neuroendocrine tumour of the skin. Remission rates are high with chemotherapy in patients with metastasis, but without any improvement in overall survival.We present the case of a 90-year-old woman with facial mcc. After radiation and surgery, the mcc recurred with widespread cutaneous and regional lymph node metastases. The metastases were treated with weekly intralesional injections of 1-2×10 6 IU interferon alfa-2a, accompanied by topical imiquimod 5% cream 3 times weekly. After partial regression, subcutaneous pegylated interferon alfa-2b was added at a dose of 30 μg weekly, which was then increased to 50 μg weekly. At 4 months after the start of immunotherapy, all cutaneous metastases and the intralesionally treated lymph node metastases receded. Interruption or reduction of systemic interferon application resulted in locoregional relapses that were successfully treated with surgery or intralesional interferon injections. The patient remains alive 30 months after initiation of immunotherapy, suggesting that locally metastasized mcc might be able to be controlled with local and systemic immunotherapy.

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“…Moreover, the data from a Phase Ⅰ/Ⅱ study of a combination of topical imiquimod and intralesional IL-2 have also revealed that its treatment induced a significant clinical response in patients with multiple accessible melanoma metastases by increasing the activated lymphocytes and the production of IFN-γ by peripheral blood mononuclear cells as well as by restoring the Th1/Th2 balance [110,111] . In addition, a therapeutic treatment consisting of an adjuvant immunotherapy with high doses of immunosuppressive agents, IL-2 and/or IFN-α, alone or in combination with chemotherapy or adoptive cell therapy, has also been observed to result in a complete and long-lasting remission in a small subset of melanoma patients [1,9,10,66,113,116,117,[128][129][130] .…”

Section: Immunotherapy-based Strategiesmentioning

confidence: 99%

“…In addition, several clinical trials have also been carried out or are undergoing to investigate the anticarcinogenic efficacy of new chemopreventive and anticarcinogenic agents and diverse immunosuppressive therapeutic strategies such as the use of dentritic cells, high-doses of interferon-α (IFN-α) and/or IL-2 and anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibody, alone or in combination with current therapies for treating locally advanced, metastatic and recurrent melano-mas [33,66,[107][108][109][110][111][112][113][114][115][116][117][118][119] . The cytotoxic drugs include the specific inhibitors of B-Raf E600V , N-Ras G61K , KIT, EGFR and hedgehog signaling elements.…”

Section: Molecular Targeting Strategiesmentioning

confidence: 99%

Novel biomarkers and therapeutic targets for optimizing the therapeutic management of melanomas

Mimeault

Batra²

2012

WJCO

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Cutaneous malignant melanoma is the most aggressive form of skin cancer with an extremely poor survival rate for the patients diagnosed with locally invasive and metastatic disease states. Intensive research has led in last few years to an improvement of the early detection and curative treatment of primary cutaneous melanomas that are confined to the skin by tumor surgical resection. However, locally advanced and disseminated melanomas are generally resistant to conventional treatments, including ionizing radiation, systemic chemotherapy, immunotherapy and/or adjuvant stem cellbased therapies, and result in the death of patients. The rapid progression of primary melanomas to locally invasive and/or metastatic disease states remains a major obstacle for an early effective diagnosis and a curative therapeutic intervention for melanoma patients. Importantly, recent advances in the melanoma research have led to the identification of different gene products that are often implicated in the malignant transformation of melanocytic cells into melanoma cells, including melanoma stem/progenitor cells, during melanoma initiation and progression to locally advanced and metastatic disease states. The frequent deregulated genes products encompass the oncogenic B-RafV600E and N-RasQ61R mutants, different receptor tyrosine kinases and developmental pathways such as epidermal growth factor receptor (EGFR), stem cell-like factor (SCF) receptor KIT, hedgehog, Wnt/β-catenin, Notch, stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor-4 (CXCR4) and vascular endothelial growth factor (VEGF)/ VEGFR receptor. These growth factors can cooperate to activate distinct tumorigenic downstream signaling elements and epithelial-mesenchymal transition (EMT)-associated molecules, including phosphatidylinositol 3'-kinase (PI3K)/Akt/ molecular target of rapamycin (mTOR), nuclear factor-kappaB (NF-κB), macrophage inhibitory cytokine-1 (MIC-1), vimentin, snail and twist. Of therapeutic relevance, these deregulated signal transduction components constitute new potential biomarkers and therapeutic targets of great clinical interest for improving the efficacy of current diagnostic and prognostic methods and management of patients diagnosed with locally advanced, metastatic and/or relapsed melanomas.

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Topical imiquimod and intralesional interleukin-2 increase activated lymphocytes and restore the Th1/Th2 balance in patients with metastatic melanoma

Cited by 46 publications

References 36 publications

Treatment Failure of a TLR-7 Agonist Occurs Due to Self-Regulation of Acute Inflammation and Can Be Overcome by IL-10 Blockade

Treatment Failure of a TLR-7 Agonist Occurs Due to Self-Regulation of Acute Inflammation and Can Be Overcome by IL-10 Blockade

Immunotherapy with Imiquimod and Interferon Alfa for Metastasized Merkel Cell Carcinoma

Novel biomarkers and therapeutic targets for optimizing the therapeutic management of melanomas

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