WT1-pulsed Dendritic Cell Vaccine Combined with Chemotherapy for Resected Pancreatic Cancer

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Summary

Wilms’ tumor 1 (WT1) is a tumor-linked antigen highly expressed in cancer. We examined the safety of WT1-peptide pulsed dendritic cell (WT1-DC) vaccine in combination with chemotherapy in patients with surgically resected pancreatic cancer. immunotherapy has been put forward as a new treatment approach for such cancer types with poor prognosis, and various methods have been examined in practice. the result of This study clarified the potential acquisition of immunity after vaccination targeting WT1.

Introduction

Wilms’ tumor 1 WT1 is a tumor-associated antigen highly expressed in cancer. To examine the safety of WT1-peptide pulsed dendritic cell (WT1-DC) vaccine in combination with chemotherapy in patients with surgically resected pancreatic cancer.

Eight patients aged 20-70 years, with resectable pancreatic cancer undergoing surgery either combined with S-1 or S-1 plus gemcitabine therapy were enrolled in the study.

Methodology

• Immature DCs were generated by culturing adherent cells in AIM-V medium containing GM-CSF and IL-4 for 5 days using mononuclear cell-rich fraction.
• Mature DCs were differentiated from immature DC by stimulation of OK-432 and PGE2 for 24 hours.
• For each vaccination, an aliquot of frozen mDC’s was thawed immediately prior to clinical use and primed with 100 g/mL of good manufacturing practice-grade WT1 peptide at
40C for 30 minutes.
• Washed twice with removing free peptides, then resuspend in 1 mL of 1-2 KE of OK-432.

Treatment

Wilms’ tumor 1 (WT1) WT1-peptide pulsed dendritic cell (WT1-DC) vaccine in combination with chemotherapy in patients with surgically resected pancreatic cancer. The vaccine was intradermally and bilaterally administered near the
axillary region and groin. As a course, it was administered seven times every 2 weeks.

Results

Adverse events: Reactions at the injection site were observed in all 8 patients and all were grade I and reversible. Grade I fever was observed in five patients, and the fever quickly declined with only symptomatic treatment. No other adverse events were observed.

Analysis of WT1-specific CTLs before and after administration of WT1-DC vaccine.
Statistical analysis showed no significant difference in the tetramer assay results before and after WT1-DC vaccination in five patients (p=0.1250). On the other hand, a significant rise in score was observed on comparison of ELISPOT
assay results for all patients (p=0.0156). One patient (no. 5) without any WT1-specific immune response showed rapid recurrence of pancreatic cancer and died at 330 days.

WT1-specific cytotoxic T-lymphocytes were detected in seven patients, and WT1 and human leukocyte antigen class I antigens were positive in all cases. Of the eight patients, four died because of recurrence and disease progression
after completion of vaccine administration, and four are currently alive. Overall survival at 2 years after the operation was 62.5±17.1% (95% confidence interval).

No serious side-effects were observed, except grade I fever in five and grade I reactions at the injection site in all patients.

Conclusion

This study clarified the safety and potential acquisition of immunity after vaccination targeting WT1. Further efficacy of WT1-DC vaccine to improve prognosis would be determined by a prospective clinical trial for resectable pancreatic
cancer.

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Scientific article publishing date : 21/2/2018

Immucura identifier : BSC21_022EN

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