title: A clinical grade poly I:C-analogue (Ampligen) promotes optimal DC maturation and Th1-type T cell responses of healthy donors and cancer patients in vitro.
abstract: Maturation of dendritic cells (DC) can be triggered in vitro by inflammatory cytokines or Toll-like receptor (TLR) ligands such as CpG or polyI:C. Corresponding, well-characterized agents which can be applied in clinical settings are sparse. We have evaluated a clinical grade, non-toxic analogue of polyI:C, poly(I:C12U) (Ampligen), as a potential adjuvant for cancer immunotherapy, for its ability to drive maturation of human myeloid DC. Our results provide evidence that poly(I:C12U) is effective in inducing optimal phenotypic (elevated levels of MHC-Class I/Class II, CD83, CCR7, CD86 and CD40 molecules) and functional maturation of human DC in vitro, capable of promoting the production of the inflammatory (Th1-type) cytokine IL-12, with significantly lower levels of IL-10 production, compared to that induced by the parent compound polyI:C. Importantly, poly(I:C12U) has a comparable effect on the maturation and function of DC derived either from healthy donors or cancer patients indicating that it is able to overcome any immune suppressive factors associated with the tumour bearing state. These characteristics make poly(I:C12U) a suitable agent for use as an adjuvant in cancer directed immunotherapeutic regimes.
authors.affiliation: Velindre Cancer Centre, Velindre NHS Trust, Cardiff, UK. Hossein.Navabi@velindre-tr.wales.nhs.uk
authors.forename: H
authors.initials: H
authors.lastname: Navabi
authors.forename: B
authors.initials: B
authors.lastname: Jasani
authors.forename: A
authors.initials: A
authors.lastname: Reece
authors.forename: A
authors.initials: A
authors.lastname: Clayton
authors.forename: Z
authors.initials: Z
authors.lastname: Tabi
authors.forename: C
authors.initials: C
authors.lastname: Donninger
authors.forename: M
authors.initials: M
authors.lastname: Mason
authors.forename: M
authors.initials: M
authors.lastname: Adams
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000276:immunology / Q000628:therapy; D011070:Poly I-C / Q000494:pharmacology*; D011072:Poly U / Q000494:pharmacology*; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology; D014019:Tissue Donors
chemical_list: D000998:Antiviral Agents; D011072:Poly U; C047490:poly(I).poly(c12,U); D011070:Poly I-C