Immunological Response after Therapeutic Vaccination with WT1 mRNA-loaded Dendritic Cells in End-stage Endometrial Carcinoma
WT1
Summary
The study investigated whether WT1 immunotherapy may present an attractive treatment option. for patients with uterine cancer. This is the first patient with a WT1-positive endometrial carcinoma, to receive immunotherapy with WT1-RNA-loaded dendritic cells, resulting in a vaccine-specific T cell response.
Patients characteristics
A 45 years old was diagnosed with stage IV Serous Endometrial Cancer. Underwent 3 cycles of Chemotherapy, underwent interval debulking surgery with no residual tumor.
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
• At the start of the vaccination, she was no complaint. Her Karnofsky Performance Scale (KPS) was 60 with a general health and quality of life estimation of 3 at a scale ranging from 1(very bad) to 7 (excellent) • After 2nd vaccination, indicated her general health and QoL estimation of 4 and tumor marker started to decrease and WT1-specific T-cells increased 2.5 fold.
• After 3rd vaccination, she showed more dyspnea, KPS was 50 and general health and QoL was again 3.
• No vaccine-related toxicities were observed.
• The treatment was feasible and there were no treatment-related side-effects.
Conclusion
This is the first patient with a WT1-positive endometrial carcinoma, to receive immunotherapy with WT1-RNA-loaded dendritic cells, resulting in a vaccine-specific T cell response.