A Phase I/II Clinical Trial Wilms’ Tumor Gene 1 (WT1) – loaded Dendritic Cell Immunotherapy in Patients with Uterine Tumors

uterus

Uterus

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Summary

In this study pre-treated patients uterine cancer received vaccines of autologous dendritic cells (DCs) electroporated with WT1 mRNA. Safety, feasibility and immunogenicity were assessed. Oncological and immunological responses were observed and are supportive for further research.

Patients characteristics

• 2 patients with stage 1 Leiomyosarcoma (LMS)
• 2 patients with stage IV and IIIC Serous Endometrial Cancer (SEC)
• 1 patient with stage IV Leiomyosarcoma (LMS)
• 1 patient with stage III Serous Endometrial Cancer.

Methodology

• Patients underwent leukapheresis to obtain peripheral blood mononuclear cells.
• For each vaccine PBMC were thawed and seeded in culture flasks, on average
1×109 PBMCs were cultured every vaccination
• After adherence, monocytes were differentiated to immature DC, in the
presence of recombinant IL-4 and GM-CSF
• On day 6, imDC were electroporated with WT1-RNA
• Electroporated DCs were put back in culture in the presence of TNF- and IL-1
• On day 7, mDC-WT1-RNA was harvested, resuspended in DPBS with 2.5% human
serum albumin.

Treatment

The vaccine was administered intradermally (ID) in the patient’s groin 1 injection per week for 4-8 weeks. Before and after injection, the patient applied Imiquimod cream at the site of injection.

Results

• All patients showed redness at the site of injection
• `1 patient with LMS had a local allergic reaction to the Imiquimod cream was then replaced by addition of prostaglandin E2 in 3rd and 4th vaccination
• 1 patient with stage IV SEC showed a transient molecular response after 4 vaccinations
• Patients with stage I and IV LMS showed radiological response
• Oncological response was observed in end-stage patients both received subsequent Chemotherapy leading to survive.
• Stage IV SEC, IIIC SEC, I LMS showed immunologic response.
Stage IV SEC – KPS- 30, HQOL-3, PFS(months)-6, Survival(months)-10, OS(months)-36 StageIIIC- KPS-80, HQOL-5, PFS(months)-3, Survival(months)-4, OS(months)-43 StageI LMS- KPS-90, HQOL-7, PFS(months)-2, Survival(months)-4, OS(months)-22 StageI LMS- KPS-90, HQOL-5, PFS(months)-0, Survival(months)-3, OS(months)-20 Stage III SEC- KPS-50, HQOL-2, PFS(months)-0, Survival(months)-0, OS(months)-42 .

Conclusion

This study presents promising results of the first six patients with uterine cancer to be treated with autologous DCs loaded with WT1 mRNA. The technique is feasible and safe. All transient oncological reactions were seen in the HLA-A2-positive patients and matched the immunological response in two out of three patients.

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Scientific article publishing date: 10/28/2013

Immucura identifier BSC21_316EN

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