Treatment of Stage IA Cutaneous T-Cell Lymphoma With Topical Application of the Immune Response Modifier Imiquimod

TLR7 and TLR8 as targets in cancer therapy

“…In addition, several controlled clinical trials as well as many smaller series of cases and case reports have demonstrated that imiquimod is also effective against a variety of primary skin cancers as well as cutaneous metastases of some malignancies. Cutaneous tumors that have responded well to topical treatment with imiquimod include basal cell carcinomas (Sterry et al, 2002;BathHextall et al, 2004;Geisse et al, 2004;Gollnick et al, 2005;Schulze et al, 2005), keratoacanthomas (Dendorfer et al, 2003;Peris et al, 2003), actinic keratoses (Stockfleth et al, 2001(Stockfleth et al, , 2002Lebwohl et al, 2004;Szeimies et al, 2004;Korman et al, 2005) and Bowen's disease (the latter two entities represent epidermal carcinoma in situ) (Patel et al, 2006;Peris et al, 2006), cutaneous metastases of melanoma (Steinmann et al, 2000;Bong et al, 2002;Ugurel et al, 2002;Wolf et al, 2003;Zeitouni et al, 2005), some cases of primary melanoma in situ (Fleming et al, 2004;Kamin et al, 2005;Ray et al, 2005;Wolf et al, 2005;Lonsdale-Eccles et al, 2006) and cutaneous T-cell lymphomas (Suchin et al, 2002;Dummer et al, 2003b;Chong et al, 2004;Deeths et al, 2005). Clinical responses of cutaneous neoplasias to topical treatment with imiquimod have also been observed in difficult-to-treat patient populations, such as organ transplant patients under immunosuppressive therapy (Smith et al, 2001;Prinz et al, 2004;Brown et al, 2005) or Xeroderma pigmentosum patients suffering from rapid development of multiple UV-induced cutaneous malignancies …”

Immunopathogenesis and therapy of cutaneous T cell lymphoma

“…These include the administration of a variety of TLR ligands, which are presently in clinical development (87,88). Imiquimod, a member of the imidazoquinoline family, which has been approved by the FDA for the treatment of basal cell carcinoma, actinic keratoses, and condyloma, has recently been demonstrated to exhibit substantial clinical activity when applied topically to skin lesions of MF patients (89,90). Imiquimod potently triggers TLR-7, which results in IFN-α and TNF-α production (91,92).…”

The beauty of TLR agonists for CTCL

“…Imiquimod, a TLR7 agonist in the imidazoquinoline family, when applied as a cream directly to CTCL skin lesions can induce local immune activation that can be associated with lesion regression. 3 However, it has quite a low bioavailability leading to inconsistency of clinical response. Moreover, responses are critically dependent on numbers of resident pDCs within lesions that can be activated by imiquimod.…”