title: Safety, immune and clinical responses in metastatic melanoma patients vaccinated with a long peptide derived from indoleamine 2,3-dioxygenase in combination with ipilimumab.
abstract: Indoleamine 2,3-dioxygenase (IDO) is an emerging new target in cancer therapy that can be targeted with active immunotherapy (e.g. through peptide vaccination). Furthermore, IDO has been identified as a key mechanism underlying resistance to treatment with the checkpoint blocking antibody ipilimumab (ipi).
  
  
  
  Ten patients with metastatic melanoma participated in a phase I first-in-human clinical study assessing safety of combining ipi with a 21-mer synthetic peptide vaccine from IDO denoted IDOlong. Secondary and tertiary end points included vaccine and clinical response.
  
  
  
  Treatment was generally safe and well tolerated. Vaccine related adverse reactions included grade I and II erythema, oedema and pruritus at the vaccination site, which were manageable with mild topical corticosteroids. One patient developed presumed ipi-induced colitis. It initially responded to high-dose parenteral corticosteroids but later relapsed while the patient was admitted to a local hospital, where he died after receiving suboptimal therapy. Vaccine-specific T-cell responses were detectable ex vivo in three patients. At first evaluation, five of the 10 treated patients were in stable disease, one of whom had an unconfirmed partial response.
  
  
  
  Treatment with IDOlong synthetic peptide vaccine in combination with ipi was generally safe and without augmented toxicity. The vaccine induced readily detectable T-cell responses in a subset of patients. Treatment showed signs of clinical activity, although not exceeding efficacy of ipi alone. Results should be confirmed in a larger study.
authors.affiliation: Center for Cancer Immune Therapy, Herlev Hospital, University of Copenhagen, Herlev, Denmark; Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: Jon
authors.initials: J
authors.lastname: Bjoern
authors.affiliation: Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: Trine Zeeberg
authors.initials: TZ
authors.lastname: Iversen
authors.affiliation: Center for Cancer Immune Therapy, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: Nikolaj Juul
authors.initials: NJ
authors.lastname: Nitschke
authors.affiliation: Center for Cancer Immune Therapy, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: Mads Hald
authors.initials: MH
authors.lastname: Andersen
authors.affiliation: Center for Cancer Immune Therapy, Herlev Hospital, University of Copenhagen, Herlev, Denmark; Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, Denmark. Electronic address: inge.marie.svane@regionh.dk.
authors.forename: Inge Marie
authors.initials: IM
authors.lastname: Svane
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects*; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000009:adverse effects* / Q000276:immunology; D005260:Female; D006801:Humans; D016233:Immunotherapy, Active / Q000379:methods; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000737:chemistry / Q000276:immunology*; D000074324:Ipilimumab; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D010865:Pilot Projects; D012878:Skin Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D019496:Cancer Vaccines; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D000074324:Ipilimumab; D010446:Peptide Fragments
keywords: IDO; Indoleamine 2,3-Dioxygenase; Ipilimumab; Melanoma; Peptide vaccine