title: Vaccination of advanced prostate cancer patients with PSCA and PSA peptide-loaded dendritic cells induces DTH responses that correlate with superior overall survival.
abstract: Prostate stem cell antigen (PSCA) and prostate-specific antigen (PSA) are overexpressed in most prostate cancers. PSCA- and PSA-derived, HLA-A2 binding peptides are specific targets for T-cell responses in vitro. A phase I/II trial was performed to demonstrate feasibility, safety and induction of antigen-specific immunity by vaccination with dendritic cells (DC) presenting PSCA and PSA peptides in patients with hormone- and chemotherapy-refractory prostate cancer. Patients received 4 vaccinations with a median of 2.7 x 10(7) peptide-loaded mature DC s.c. in biweekly intervals. Clinical responses were assessed 2 weeks after the 4th vaccination. Immune monitoring was performed by DTH and HLA multimer analysis. Twelve patients completed vaccination without relevant toxicities. Six patients had stable disease after 4 vaccinations. One patient had a complete disappearance of lymphadenopathy despite rising PSA. Four patients with SD and 1 progressor developed a positive DTH after the 4th vaccination. With a median survival of all patients of 13.4 months, DTH-positivity was associated with significantly superior survival (p = 0.003). HLA tetramer analysis detected high frequencies of peptide-specific T cells after 2 vaccinations in 1 patient who was also the sole responder to concomitant hepatitis B vaccination as an indicator of immune competence and survived 27 months after start of vaccination. Vaccination with PSA/PSCA peptide-loaded, autologous DCs may induce cellular responses primarily in immunocompetent patients, which appear to be associated with clinical benefit. Testing of DC-based vaccination is warranted for patients at earlier stages of prostate cancer.
authors.affiliation: Department of Hematology/Oncology, Freiburg University Medical Center, D-79106 Freiburg, Germany.
authors.forename: Anna-K
authors.initials: AK
authors.lastname: Thomas-Kaskel
authors.forename: Robert
authors.initials: R
authors.lastname: Zeiser
authors.forename: Rosa
authors.initials: R
authors.lastname: Jochim
authors.forename: Christian
authors.initials: C
authors.lastname: Robbel
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schultze-Seemann
authors.forename: Cornelius F
authors.initials: CF
authors.lastname: Waller
authors.forename: Hendrik
authors.initials: H
authors.lastname: Veelken
mesh_terms: D000368:Aged; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D003713:Dendritic Cells; D018572:Disease-Free Survival; D005240:Feasibility Studies; D058851:GPI-Linked Proteins; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000276:immunology*; D018579:Patient Selection; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D016019:Survival Analysis
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C110843:PSCA protein, human; D017430:Prostate-Specific Antigen