The Prostate · 2006 · 125 citations · 46 references
MedicineImmunologyOncologyCancer ImmunologyImmunotherapyVaccinologyCancer ImmunotherapyCancer VaccinesTherapeutic VaccinationTherapeutic VaccinesTumor-associated AntigensVaccine-based ImmunotherapyDendritic Cell TargetingImmunological AssaysPartial Response AssessmentPeptide VaccinationProstate Cancer ImmunotherapyProstate-specific Antigen - Targeted TherapyProstate-specific Membrane Antigen TargetingProstatic Immune Response
BACKGROUND: Immunotherapies might represent promising alternatives for the treatment of patients with hormone-refractory prostate cancer (HRPC). In a Phase I clinical trial, we evaluated a vaccination with dendritic cells (DCs) loaded with a cocktail consisting of HLA-A*0201-restricted peptides derived from five different prostate cancer-associated antigens [prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA), survivin, prostein, transient receptor potential p8 (trp-p8)]. METHODS: Eight HRPC patients received a total of four vaccinations every other week. Clinical and immunological responses were monitored by the determination of the serum PSA levels and by enzyme linked immunospot (ELISPOT) analyses, respectively. RESULTS: Apart from local skin reactions no side effects were noted. One patient displayed a partial response (PR; PSA decrease >50%) and three other patients showed stable PSA values or decelerated PSA increases. In ELISPOT analyses, three of four PSA responders also showed antigen-specific CD8+ T-cell activation against prostein, survivin, and PSMA. CONCLUSIONS: The described protocol represents a safe and feasible concept for the induction of clinical and immunological responses. The application of a peptide cocktail-derived from different antigens as a novel treatment modality is supposed to allow for the genetic and biologic heterogeneity of PCa.
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