title: Phase I/IIa clinical trial of a novel hTERT peptide vaccine in men with metastatic hormone-naive prostate cancer.
abstract: In newly diagnosed metastatic hormone-naive prostate cancer (mPC), telomerase-based immunotherapy with the novel hTERT peptide vaccine UV1 can induce immune responses with potential clinical benefit. This phase I dose escalation study of UV1 evaluated safety, immune response, effects on prostate-specific antigen (PSA) levels, and preliminary clinical outcome. Twenty-two patients with newly diagnosed metastatic hormone-naïve PC (mPC) were enrolled; all had started androgen deprivation therapy and had no visceral metastases. Bone metastases were present in 17 (77%) patients and 16 (73%) patients had affected lymph nodes. Three dose levels of UV1 were given as intradermal injections combined with GM-CSF (Leukine®). Twenty-one patients in the intention-to-treat population (95%) received conformal radiotherapy. Adverse events reported were predominantly grade 1, most frequently injection site pruritus (86.4%). Serious adverse events considered possibly related to UV1 and/or GM-CSF included anaphylactic reaction in two patients and thrombocytopenia in one patient. Immune responses against UV1 peptides were confirmed in 18/21 evaluable patients (85.7%), PSA declined to <0.5 ng/mL in 14 (64%) patients and in ten patients (45%) no evidence of persisting tumour was seen on MRI in the prostatic gland. At the end of the nine-month reporting period for the study, 17 patients had clinically stable disease. Treatment with UV1 and GM-CSF gave few adverse events and induced specific immune responses in a large proportion of patients unselected for HLA type. The intermediate dose of 0.3 mg UV1 resulted in the highest proportion of, and most rapid UV1-specific immune responses with an acceptable safety profile. These results warrant further clinical studies in mPC.
authors.affiliation: Department of Oncology and Radiotherapy, Oslo University Hospital-Radiumhospitalet, PO Box 4953, Nydalen, 0424, Oslo, Norway. Wolfgang.lilleby@ous-hf.no.
authors.forename: Wolfgang
authors.identifier: http://orcid.org/0000-0002-8390-9353
authors.initials: W
authors.lastname: Lilleby
authors.affiliation: Section for Cancer Immunology, Oslo University Hospital-Radiumhospitalet, Oslo, Norway.|Ultimovacs AS, Oslo, Norway.
authors.forename: Gustav
authors.initials: G
authors.lastname: Gaudernack
authors.affiliation: Department for Clinical Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway.
authors.forename: Paal F
authors.initials: PF
authors.lastname: Brunsvig
authors.affiliation: Department of Pathology, Oslo University Hospital-Radiumhospitalet, Oslo, Norway.
authors.forename: Ljiljana
authors.initials: L
authors.lastname: Vlatkovic
authors.affiliation: Department for Clinical Cancer Research, Oslo University Hospital-Radiumhospitalet, Oslo, Norway.
authors.forename: Melanie
authors.initials: M
authors.lastname: Schulz
authors.affiliation: Department of Oncology and Radiotherapy, Oslo University Hospital-Radiumhospitalet, PO Box 4953, Nydalen, 0424, Oslo, Norway.
authors.forename: Kate
authors.initials: K
authors.lastname: Mills
authors.affiliation: Department of Radiology, Oslo University Hospital-Radiumhospitalet, Oslo, Norway.
authors.forename: Knut Håkon
authors.initials: KH
authors.lastname: Hole
authors.affiliation: Department of Cellular Therapy, Oslo University Hospital-Radiumhospitalet, Oslo, Norway.
authors.forename: Else Marit
authors.initials: EM
authors.lastname: Inderberg
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D000368:Aged; D001859:Bone Neoplasms / Q000556:secondary; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D015331:Cohort Studies; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D007110:Immunity, Active / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D008207:Lymphatic Metastasis; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D017430:Prostate-Specific Antigen / Q000097:blood* / Q000276:immunology; D011471:Prostatic Neoplasms / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D019098:Telomerase / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D022223:Vaccines, Subunit / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use
chemical_list: D019496:Cancer Vaccines; D010446:Peptide Fragments; D011994:Recombinant Proteins; C000622647:UV1 vaccine; D022223:Vaccines, Subunit; C081222:sargramostim; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019098:Telomerase; D017430:Prostate-Specific Antigen
keywords: Cancer vaccine; Immune response; Prostate cancer; hTERT