Vaccination of hormone-refractory prostate cancer patients with peptide cocktail-loaded dendritic cells: results of a phase I clinical trial.
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.
Fuessel
Susanne
S
Department of Urology, Medical Faculty, Technical University Dresden, Dresden, Germany.
Meye
Axel
A
Schmitz
Marc
M
Zastrow
Stefan
S
Linné
Clemens
C
Richter
Katja
K
Löbel
Barbel
B
Hakenberg
Oliver W
OW
Hoelig
Kristina
K
Rieber
E Peter
EP
Wirth
Manfred P
MP
D000368:Aged; D000954:Antigens, Surface / Q000032:analysis / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000276:immunology*; D019008:Drug Resistance, Neoplasm; D043425:Glutamate Carboxypeptidase II / Q000032:analysis / Q000276:immunology; D015234:HLA-A Antigens / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D015789:HLA-A2 Antigen; D006801:Humans; D007124:Immunoenzyme Techniques; D018189:Immunomagnetic Separation; D016233:Immunotherapy, Active; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000276:immunology; D008869:Microtubule-Associated Proteins / Q000032:analysis / Q000276:immunology; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis / Q000276:immunology; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D000077022:Survivin; D050053:TRPM Cation Channels / Q000032:analysis / Q000276:immunology
D000954:Antigens, Surface; C107489:BIRC5 protein, human; D019496:Cancer Vaccines; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D051034:Inhibitor of Apoptosis Proteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; D050053:TRPM Cation Channels; C425966:TRPM8 protein, human; C422655:prostein; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II; D017430:Prostate-Specific Antigen