Vaccination of advanced prostate cancer patients with PSCA and PSA peptide-loaded dendritic cells induces DTH responses that correlate with superior overall survival
| Autor: | Anna-K. Thomas-Kaskel, Cornelius F. Waller, Christian Robbel, Robert Zeiser, Rosa Jochim, Wolfgang Schultze-Seemann, Hendrik Veelken |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Cancer Research medicine.medical_treatment GPI-Linked Proteins Cancer Vaccines Disease-Free Survival Prostate cancer Immune system Antigen Prostate Antigens Neoplasm medicine Humans Prospective Studies Aged Membrane Glycoproteins business.industry Patient Selection Prostatic Neoplasms Immunotherapy Dendritic Cells Middle Aged Prostate-Specific Antigen medicine.disease Survival Analysis Prostate Stem Cell Antigen Neoplasm Proteins Vaccination Prostate-specific antigen medicine.anatomical_structure Oncology Immunology Feasibility Studies business |
| Zdroj: | International journal of cancer. 119(10) |
| ISSN: | 0020-7136 |
| Popis: | 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 × 107 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. © 2006 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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