Vaccination of advanced prostate cancer patients with PSCA and PSA peptide-loaded dendritic cells induces DTH responses that correlate with superior overall survival
✍ Scribed by Anna-K. Thomas-Kaskel; Robert Zeiser; Rosa Jochim; Christian Robbel; Wolfgang Schultze-Seemann; Cornelius F. Waller; Hendrik Veelken
- Publisher
- John Wiley and Sons
- Year
- 2006
- Tongue
- French
- Weight
- 257 KB
- Volume
- 119
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
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 × 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. © 2006 Wiley‐Liss, Inc.