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

Tryggestad, Anne Merete Aaland; Bigalke, Iris; Lilleby, Wolfgang; Axcrona, Karol; Hønnåshagen, Turid K; Skoge, Lisbeth; Sæbøe-Larssen, Stein; Solum, Guri; Olaussen, Richard W.; Josefsen, Dag; Schendel, Dolores; Kvalheim, Gunnar

doi:10.26502/jcsct.5079081

Cited by 1 publication

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“…Cancer‐peptide vaccines that targeted hTERT successfully treated metastatic, hormone‐naïve PC 8 . Similarly, we previously demonstrated that DC vaccines against hTERT and Survivin antigens showed encouraging clinical effects in metastatic PC 9 …”

Section: Introductionmentioning

confidence: 65%

“…We previously reported that long‐term use of DC vaccines that targeted hTERT and Survivin had beneficial clinical effects in metastatic PC 9 . In the current study, we decided to add a vaccine of DCs transfected with mRNA from autologous tumor tissue.…”

Section: Discussionmentioning

confidence: 99%

“…The protocols for vaccine production from DCs were changed due to new developments. First, the 6‐day protocol for producing DCs was reduced to 3 days by transfecting mature Oslo fast DCs with mRNA 9,17 . Second, the Oslo fast DCs were replaced with Munich fast DCs, treated with a maturation cocktail that included a toll‐like receptor 7/8 agonist 18,19 …”

Section: Methodsmentioning

confidence: 99%

“…Quality control, including the confirmation of maturation marker expression, was performed with FACS analysis, cytokine production analysis (Signal 3‐assay and ELISA), and a migration capacity test, as described previously 9 …”

Section: Methodsmentioning

confidence: 99%

“…Based on RNA sequencing of tumor tissues from three individual patients (data not shown), we found that several tumor antigens associated with PC were expressed, including STEAP1, PSMA1, and PAP 6,20,21 . We used PepTivator® peptide pools of hTERT, Survivin, PSMA1, STEAP1, and PAP (Miltenyi Biotech) to assess T‐cell responses, as previously described, 9 at 7 weeks after RALP (baseline response) and at one‐time point during the vaccination period (Figures 2 and ).…”

Section: Methodsmentioning

confidence: 99%

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Long‐term first‐in‐man Phase I/II study of an adjuvant dendritic cell vaccine in patients with high‐risk prostate cancer after radical prostatectomy

Tryggestad

Axcrona

et al. 2021

The Prostate

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Background Patients with high‐risk prostate cancer (PC) can experience biochemical relapse (BCR), despite surgery, and develop noncurative disease. The present study aimed to reduce the risk of BCR with a personalized dendritic cell (DC) vaccine, given as adjuvant therapy, after robot‐assisted laparoscopic prostatectomy (RALP). Methods Twelve weeks after RALP, 20 patients with high‐risk PC and undetectable PSA received DC vaccinations for 3 years or until BCR. The primary endpoint was the time to BCR. The immune response was assessed 7 weeks after surgery (baseline) and at one‐time point during the vaccination period. Results Among 20 patients, 11 were BCR‐free over a median of 96 months (range: 84–99). The median time from the end of vaccinations to the last follow‐up was 57 months (range: 45–60). Nine patients developed BCR, either during (n = 4) or after (n = 5) the vaccination period. Among five patients diagnosed with intraductal carcinoma, three experienced early BCR during the vaccination period. All patients that developed BCR remained in stable disease within a median of 99 months (range: 74–99). The baseline immune response was significantly associated with the immune response during the vaccination period (p = 0.015). For patients diagnosed with extraprostatic extension (EPE), time to BCR was longer in vaccine responders than in non‐responders (p = 0.09). Among 12 patients with the International Society of Urological Pathology (ISUP) grade 5 PC, five achieved remission after 84 months, and all mounted immune responses. Conclusion Patients diagnosed with EPE and ISUP grade 5 PC were at particularly high risk of developing postsurgical BCR. In this subgroup, the vaccine response was related to a reduced BCR incidence. The vaccine was safe, without side effects. This adjuvant first‐in‐man Phase I/II DC vaccine study showed promising results. DC vaccines after curative surgery should be investigated further in a larger cohort of patients with high‐risk PC.

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Section: Introductionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 99%