gms | German Medical Science

Purpose: We conducted a pilot trial to evaluate the feasibility and tolerability of a prime/boost vaccine strategy using autologous dendritic cells (DC) loaded with PSA-peptides after prestimulation with Interferone-gamma (INF-γ) for patients with hormone refractory prostate carcinoma. The induction of PSA-specific immunity and clinical response was also evaluated.

Patients and Methods: Fifeteen HLA-A2 positive patients with hormone-refractory, metastatic prostate cancer were vaccinated for four times with intracutaneously applicated PSA-peptide loaded DC after prestimulation with INF-γ (50 µg/m² KO). Primary end points were response rate (NPCP), development of PSA and clinical benefit (pain intensity). Secondary end points were quality of life (EORTC QLQ-C30), safety and immunological parameters.

Results: The vaccination was well tolerated without any vaccination associated adverse events. Twelve of fifeteen patients could be fully evaluated. One patient dropped out due to early progress, one patient with tumor far in progress died tumor related and one patient was not evaluable because of radiotherapy during vaccination. Of the 12 eligible patients two showed a PSA-decline, three a decrease in PSA-velocity, one no change and six an increase of PSA. In regard to the clinical response four patients showed stable disease, one a mixed response and one a partial response. No complete response was seen. DTH-response to PSA-loaded DC was strongly positive for nine of the vaccinated patients. The statistical evaluation of ELISPOT and Tetramer testing is still in progress. First results show some hints for correlation between PSA-specific T-cell activation and PSA-velocity.

Conclusion: Therapy with PSA-Peptide loaded dendritic cells after prestimulation with INF-γ was feasible and associated with minimal toxicity. No evidence for the induction of autoimmunity could be detected. The biochemical and clinical response rate implicate a potential antitumor activity.