Imiquimod 5% cream for the treatment of superficial and nodular basal cell carcinoma: randomized studies comparing low-frequency dosing with and without occlusion

Sterry, Wolfram; Ruzicka, Thomas; Herrera, E.; Takwale, A.; Bichel, Jens; Andres, Kara L.; Ding, Lanlin; Thissen, M. R. T. M.

doi:10.1046/j.1365-2133.2002.05069.x

Cited by 178 publications

(155 citation statements)

References 7 publications

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“…We have established that PapMV is a potent TLR7 agonist that induces strong IFN-a production and broad immune cell activation. TLR7 agonists such as imidazoquinolines (like R837) have been shown to increase the efficiency of vaccines that trigger cellular immune responses against pathogens or cancer (11,(52)(53)(54)(55). However, use of imidazoquinolines is limited to specific applications such as topical creams because of their side effects and short half-life when administrated systemically (56).…”

Section: Discussionmentioning

confidence: 99%

Nanoparticle Adjuvant Sensing by TLR7 Enhances CD8+ T Cell–Mediated Protection from Listeria Monocytogenes Infection

Lebel

Daudelin

Chartrand

et al. 2014

The Journal of Immunology

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Developing new adjuvants and vaccination strategies is of paramount importance to successfully fight against many life-threatening infectious diseases and cancer. Very few adjuvants are currently authorized for human use, and these mainly stimulate a humoral response. However, specific Abs are not sufficient to confer protection against persisting infections or cancer. Therefore, development of adjuvants and immunomodulators able to enhance cell-mediated immune responses represents a major medical need. We recently showed that papaya mosaic virus nanoparticles (PapMV), self-assembled from the coat protein of a plant virus and a noncoding ssRNA molecule, are highly immunogenic in mice. PapMV can be used either as a vaccine delivery platform, through fusion of various epitopes to the coat protein or as adjuvant to enhance humoral immune responses against coadministered Ags or vaccines. However, the mechanisms that confer these immunomodulatory properties to PapMV and its ability to enhance T cell vaccines remain unknown. Using immunization studies in mice, we demonstrate in this paper that PapMV represents a novel TLR7 agonist with strong immunostimulatory properties. More importantly, pretreatment with PapMV significantly improves effector and memory CD8+ T cell responses generated through dendritic cell vaccination increasing protection against a Listeria monocytogenes challenge.

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Section: Discussionmentioning

confidence: 99%

Nanoparticle Adjuvant Sensing by TLR7 Enhances CD8+ T Cell–Mediated Protection from Listeria Monocytogenes Infection

Lebel

Daudelin

Chartrand

et al. 2014

The Journal of Immunology

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“…Various regimens of imiquimod have been used in practice, including application twice daily, once daily, and every other day; applications have been performed with and without occlusion for treatment courses ranging from 6 to 16 weeks. 45,[64][65][66][67][68][69][70][71][72][73] Overall, rates of 3-to 12-month clinical and histologic cure have been reported to range from 60% to 80% in well-designed RCTs, with the highest rates reported for shorter follow-up and clinical J AM ACAD DERMATOL VOLUME jj, NUMBER j cure. Moderate-to-severe local treatment-associated adverse events include skin redness, swelling, erosions, crusts, vesicles, itching, and, occasionally, tingling sensations.…”

Section: Topical Therapiesmentioning

confidence: 99%

Guidelines of care for the management of basal cell carcinoma

Baum¹,

Bordeaux²,

Brown³

et al. 2018

Journal of the American Academy of Dermatology

315

219

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Basal cell carcinoma (BCC) is the most common form of human cancer, with a continually increasing annual incidence in the United States. When diagnosed early, the majority of BCCs are readily treated with office-based therapy, which is highly curative. In these evidence-based guidelines of care, we provide recommendations for the management of patients with BCC, as well as an in-depth review of the best available literature in support of these recommendations. We discuss biopsy techniques for a clinically suspicious lesion and offer recommendations for the histopathologic interpretation of BCC. In the absence of a formal staging system, the best available stratification based on risk for recurrence is reviewed. With regard to treatment, we provide recommendations on treatment modalities along a broad therapeutic spectrum, ranging from topical agents and superficially destructive modalities to surgical techniques and systemic therapy. Finally, we review the available literature and provide recommendations on prevention and the most appropriate follow-up for patients in whom BCC has been diagnosed. ( J Am Acad Dermatol

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“…4 Indeed, synthetic agonists for the RNA-sensing TLR7 are now an approved treatment for certain skin cancers and in clinical development for other malignancies. [5][6][7] Ligands targeting the RLR, RIG-I, and MDA-5 are also currently under development for cancer immunotherapy. 4,8,9 To transmit intracellular signaling, RLR and TLR employ different adaptor molecules; RLR utilize MAVS, 10 whereas TLR are coupled to MyD88 with the exception of TLR3, which exclusively signals via the adaptor TRIF.…”

Section: Introductionmentioning

confidence: 99%

Reprogramming of TLR7 signaling enhances antitumor NK and cytotoxic T cell responses

et al. 2016

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Toll-like receptor (TLR) 7 agonists are effective in topical application for the immunotherapy of skin cancers, but their performance for the systemic treatment of solid tumors is limited by the development of TLR tolerance. In this study, we describe a novel strategy to overcome TLR tolerance and enhance TLR7-dependent antitumor immune responses through reprogramming of TLR signaling pathways. The sensitivity of TLR7 signaling in dendritic cells (DC) was increased by prior stimulation with the dsRNA poly (I:C) that mimics virally induced immune activation. Timing of the stimulations was important, as sequential stimulation with poly(I:C) and the TLR7 agonist R848 interspaced by 24 h induced higher MAPK and NFkB signaling in DC than the simultaneous application of the same ligands. DC activated by sequential poly(I:C)/R848 stimulation efficiently induced Th1 differentiation and primed NK-cell and cytotoxic T-cell responses. We have developed a treatment regimen taking advantage of TLR7 reprogramming that cured over 80% of large immunogenic tumors in mice by the action of NK cells and cytotoxic T cells. These results have direct implications for the use of these clinically established ligands in the immunotherapy of cancer.

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Imiquimod 5% cream for the treatment of superficial and nodular basal cell carcinoma: randomized studies comparing low-frequency dosing with and without occlusion

Cited by 178 publications

References 7 publications

Nanoparticle Adjuvant Sensing by TLR7 Enhances CD8+ T Cell–Mediated Protection from Listeria Monocytogenes Infection

Nanoparticle Adjuvant Sensing by TLR7 Enhances CD8+ T Cell–Mediated Protection from Listeria Monocytogenes Infection

Guidelines of care for the management of basal cell carcinoma

Reprogramming of TLR7 signaling enhances antitumor NK and cytotoxic T cell responses

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