Vaccination of hormone-refractory prostate cancer patients with peptide cocktail-loaded dendritic cells: Results of a phase I clinical trial

• Published in: The Prostate 2006-06, Vol.66 (8), p.811-821
• Main Authors: Fuessel, Susanne, Meye, Axel, Schmitz, Marc, Zastrow, Stefan, Linné, Clemens, Richter, Katja, Löbel, Barbel, Hakenberg, Oliver W., Hoelig, Kristina, Rieber, E. Peter, Wirth, Manfred P.
• Format: Article
• Language: English
• Subjects: Aged; Antigens, Surface - analysis; Antigens, Surface - immunology; Biological and medical sciences; Cancer Vaccines - administration & dosage; Cancer Vaccines - therapeutic use; CD8-Positive T-Lymphocytes - immunology; dendritic cells; Dendritic Cells - immunology; Drug Resistance, Neoplasm; ELISPOT assay; Glutamate Carboxypeptidase II - analysis; Glutamate Carboxypeptidase II - immunology; Gynecology. Andrology. Obstetrics; HLA-A Antigens - chemistry; HLA-A Antigens - immunology; HLA-A Antigens - therapeutic use; HLA-A2 Antigen; hormone-refractory prostate cancer; Humans; Immunoenzyme Techniques; Immunomagnetic Separation; immunotherapy; Immunotherapy, Active; Inhibitor of Apoptosis Proteins; Male; Male genital diseases; Medical sciences; Membrane Proteins - analysis; Membrane Proteins - immunology; Microtubule-Associated Proteins - analysis; Microtubule-Associated Proteins - immunology; Middle Aged; Neoplasm Proteins - analysis; Neoplasm Proteins - immunology; Nephrology. Urinary tract diseases; Prostate-Specific Antigen - blood; Prostatic Neoplasms - immunology; Prostatic Neoplasms - pathology; Prostatic Neoplasms - therapy; T-cell response; TRPM Cation Channels - analysis; TRPM Cation Channels - immunology; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/pros.20404

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. Prostate © 2006 Wiley‐Liss, Inc.