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Immunogenic Properties and Antitumor Effects of Novel Therapeutic Dendritic Cell Vaccines Expressing hTERT and Survivin Antigens in Metastatic Prostate Cancer Patients

Author(s): Anne Merete Aaland Tryggestad, Iris Bigalke, Wolfgang Lilleby, Karol Axcrona, Turid Kirsti Hønnåshagen, Lisbeth Johanne Skoge, Stein Sæbøe-Larssen, Guri Solum, Richard Wil

Objective: To investigate the clinical effects of novel therapeutic dendritic cell vaccines targeting the universal tumour antigens human telomerase reverse transcriptase and Survivin in a small exploratory group of four patients with high-risk prostate cancer who had progression after secondary therapy. In contrast to previous dendritic cell vaccine studies, we explored application of intradermal dendritic cell vaccines every month over longer periods of time to boost and maintain potential immune responses.

Methods: Dendritic cell vaccines were given in combination with androgen deprivation therapy, with and without radiotherapy and chemotherapy, until tumour progression. PSA levels were followed throughout the whole treatment period. Immune responses were assessed investigating antigen specific CD4 and CD8 T cell responses at chosen time points.

Results: Two patients remained in clinical remission at 113 and 72 months after start of dendritic cell vaccination. Time to progression for these two patients after secondary therapy, prior to dendritic cell vaccination was 3 and 7 months, respectively. A third patient obtained a stable clinical disease for 95 months with DC vaccines, androgen deprivation therapy and radiotherapy, with time to progression of only 14 months after secondary therapy but before start of vaccination. These patients mounted specific immune responses during dendritic cell vaccination as detected at several time points during treatment.

Conclusion: These results suggest that patients with low tumour burden may benefit significantly from continuous personalized dendritic cell vaccination when combined with additional therapies. Importantly, no vaccine-related toxicity was observed despite application of substantial numbers of dendritic cells over extended periods of time. These exploratory cases provide valuable information regarding further studies of dendritic cell vaccination in larger numbers of high-risk prostate cancer patients for whom prolongation of time to progression is of high medical relevance.

 

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