Imiquimod 5% cream (Aldara™)

Abstract

Imiquimod is a novel synthetic molecule with potent immune-modifying activities. Formulated in a 5% vanishing cream as Aldara, this self-applied therapy has shown good efficacy and safety in the treatment of external genital and perianal warts caused by human papillomavirus (HPV) infection (Condyloma acuminata). The molecule does not demonstrate direct antiviral activity, but through induction of cytokines results in immune-based resolution of wart tissue and reduction of viral burden. Phase III trials of imiquimod have demonstrated that patients who experience complete clearance of either new or recalcitrant warts tend to remain clear, possibly related to Th1 immune recognition and memory. Self-application, good tolerability and a unique mechanism of action combine to make imiquimod a reasonable first-line therapy for genital warts. The effects of imiquimod on immune function suggest several potential uses. Preclinical studies of infection with herpes simplex virus (HSV), cutaneous leishmaniasis, Rift Valley Fever virus and vesiculostomatitis virus have shown reduced viral persistence, reduced recurrence (HSV) and diminished pathology (Leishmania donovani). In a murine tumour model using the FCB bladder cancer cell line, imiquimod behaves as a potent adjuvant leading to immune-based tumour cell eradication and immunity against subsequent FCB cell challenge. The ability of imiquimod to induce significant production of interferon alpha (IFN-alpha) by monocytes/macrophages suggests that diseases responsive to recombinant interferon therapy, such as basal cell carcinoma, may be reasonable clinical targets. The induction of tumour necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma) and interleukin-12 (IL-12) leads to inhibition of IL-5, with animal models demonstrating immune deviation away from Th2 immune responses. The observation that several patients with hepatitis C infection and eosinophilia showed normalisation of elevated eosinophil counts in association with oral imiquimod therapy encourages further exploration of the immune modifying properties of this novel molecule. This review is focused on the use of imiquimod for the treatment of external genital and perianal warts.

Development of a novel TLR8 agonist for cancer immunotherapy

“…Second, from safety perspective, TLR8 agonists have better safety profile allowing systemic administration whereas targeting other TLRs such as TLR4, 7, TLR7/8 dual, TLR9 appear to be less tolerable when dosed systemically and are mainly dosed locally through intra-tumoral injection or limited to topical use [ 10 , 12 ]. For example, imiquimod, also known as Aldara, an approved drug predominantly targeting TLR7 is used as a topical drug because it is too toxic to use systemically, which dramatically limits its clinical application [ 25 – 27 ]. Systemic administration of TLR7 agonists has been explored using relatively low doses or prodrug form to reduce their systemic toxicity.…”

Host-Directed Antiviral Therapy

“…Another drug, podofilox (Condylox) potently inhibits cell mitosis, which eventually results in the regression of HPV-associated warts (77). In addition, imiquimod (Aldara) exhibits profound antitumor (antiwart) activity by acting on several immunological activities (78). Likewise, sinecatechins (Veregen) was the first botanical drug product approved by the FDA in 2006 for the treatment of external genital and perianal warts, although its mechanism of action is as yet not known.…”