title: Trial watch:  FDA-approved Toll-like receptor agonists for cancer therapy.
abstract: Toll-like receptors (TLRs) have first been characterized for their capacity to detect conserved microbial components like lipopolysaccharide (LPS) and double-stranded RNA, resulting in the elicitation of potent (innate) immune responses against invading pathogens. More recently, TLRs have also been shown to promote the activation of the cognate immune system against cancer cells. Today, only three TLR agonists are approved by FDA for use in humans: the bacillus Calmette-Guérin (BCG), monophosphoryl lipid A (MPL) and imiquimod. BCG (an attenuated strain of Mycobacterium bovis) is mainly used as a vaccine against tuberculosis, but also for the immunotherapy of in situ bladder carcinoma. MPL (derived from the LPS of Salmonella minnesota) is included in the formulation of Cervarix®, a vaccine against human papillomavirus-16 and -18. Imiquimod (a synthetic imidazoquinoline) is routinely employed for actinic keratosis, superficial basal cell carcinoma, and external genital warts (condylomata acuminata). In this Trial Watch, we will summarize the results of recently completed clinical trials and discuss the progress of ongoing studies that have evaluated/are evaluating FDA-approved TLR agonists as off-label medications for cancer therapy.
authors.affiliation: INSERM, U848; Villejuif, France ; Institut Gustave Roussy; Villejuif, France ; Université Paris-Sud/Paris XI; Paris, France.
authors.forename: Erika
authors.initials: E
authors.lastname: Vacchelli
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Galluzzi
authors.forename: Alexander
authors.initials: A
authors.lastname: Eggermont
authors.forename: Wolf Hervé
authors.initials: WH
authors.lastname: Fridman
authors.forename: Jerome
authors.initials: J
authors.lastname: Galon
authors.forename: Catherine
authors.initials: C
authors.lastname: Sautès-Fridman
authors.forename: Eric
authors.initials: E
authors.lastname: Tartour
authors.forename: Laurence
authors.initials: L
authors.lastname: Zitvogel
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer