WT1-mRNA dendritic cell vaccination of patients with glioblastoma multiforme, malignant pleural mesothelioma, metastatic breast cancer, and other solid tumors: type 1 T-lymphocyte responses are associated with clinical outcome

Our plain-English summary of WT1-mRNA dendritic cell vaccination of patients with glioblastoma multiforme, malignant pleural mesothelioma, metastatic breast cancer, and other solid tumors: type 1 T-lymphocyte responses are associated with clinical outcome, by Z.N. Berneman, M. De Laere, P. Germonpré, et al (Journal of Hematology & Oncology, 2025).

The study

• Authors: Z.N. Berneman, M. De Laere, P. Germonpré, M.T. Huizing, Y. Willemen, E. Lion, H. De Reu, J. Van den Bossche, J. Van den Brande, P. Specenier, S. Altintas, P.A. van Dam, N. Cools, G. Nijs, B. Stein, K. Caluwaerts, A. Snoeckx, B. Op de Beeck, K. Saevels, L. Rutsaert, I. Vandenbosch, G. Oner, M. Lammens, P. Van Damme, S. Llewellyn-Lacey, D.A. Price, Y. Oka, Y. Oji, H. Sugiyama, M.M. Couttenye, A.L. Van de Velde, V.F. Van Tendeloo, M. Peeters, S. Anguille, E.L.J.M. Smits
• Journal: Journal of Hematology & Oncology
• Published: 2025;18(1):9
• Type of article: Letter
• Cited by: 30 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Cell therapies, including tumor antigen-loaded dendritic cells used as therapeutic cancer vaccines, offer treatment options for patients with malignancies. We evaluated the feasibility, safety, immunogenicity, and clinical activity of adjuvant vaccination with Wilms' tumor protein (WT1) mRNA-electroporated autologous dendritic cells (WT1-mRNA/DC) in a single-arm phase I/II clinical study of patients with advanced solid tumors receiving standard therapy. Disease status and immune reactivity were evaluated after 8 weeks and 6 months. WT1-mRNA/DC vaccination was feasible in all patients, except one. Vaccination was well tolerated without evidence of systemic toxicity. The disease control rate and overall response rate among a total of 39 evaluable patients were 74.4% and 12.8%, respectively. Median overall survival (OS) was 43.7 months among 13 patients with glioblastoma multiforme, 41.9 months among 12 patients with metastatic breast cancer, and 48.8 months among 10 patients with malignant pleural mesothelioma, comparing favourably with historical controls reported in the literature. OS was longer in patients with stable disease at 8 weeks and disease control at 6 months versus patients without disease control at either time point. Disease control and higher OS were associated with antigen-specific type 1 CD4+ and/or CD8+ T-lymphocyte responses, mainly induced by WT1-mRNA/DC vaccination. Antigen-nonspecific type 2 CD8+ T-cell responses were common before WT1-mRNA/DC vaccination but did not show any association with clinical outcome. Collectively, these data indicate that WT1-mRNA/DC vaccination is feasible, safe, and immunogenic and shows clinical activity in patients with advanced solid tumors, suggesting that it has the potential to help improve their survival.

© 2025. The Author(s).

In plain English

This letter described a single-arm phase I/II trial of a vaccine made from patients' own dendritic cells, loaded with genetic material for the WT1 tumor protein and given as adjuvant treatment. Of 40 patients with advanced tumors, one died before vaccination, leaving 39 evaluable: 13 with glioblastoma multiforme, 12 with metastatic breast cancer, 10 with malignant pleural mesothelioma and 4 with other tumors. Vaccination was feasible in 39 of 40, with side effects limited to injection-site reactions. Disease control (response or stable disease) occurred in 25 of 39 (64.1%) at 8 weeks and 19 of 39 (48.7%) at 6 months. Median survival from diagnosis was 48.8 months in the mesothelioma group. The authors compared this with 23.4 months in earlier published research, not a control group. Disease control and survival were associated with type 1 T-cell responses. All patients with partial or complete responses also received other treatment. The authors concluded it was feasible, safe and immunogenic and showed clinical activity. They noted the patients were pre-selected and called for further studies. The article did not discuss asbestos exposure.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Single-arm (no control group) phase I/II clinical trial, reported as a short correspondence (letter to the editor)
• Who was studied: 40 patients with poor-prognosis advanced solid tumors were enrolled. One patient in the other-tumor group died before vaccination and was excluded, leaving 39 evaluable patients: 13 with glioblastoma multiforme, 12 with metastatic breast cancer, 10 with malignant pleural mesothelioma, and 4 with other tumors. The study was approved by the ethics committee of Antwerp University Hospital/University of Antwerp in Belgium. Survival was followed up to December 31, 2023. Enrollment dates are not given in the text.
• Exposure: Adjuvant treatment with WT1-mRNA/DC: autologous dendritic cells exposed to keyhole limpet hemocyanin (KLH) and electroporated with mRNA encoding the Wilms' tumor protein (WT1). Some patients also received concomitant treatment during vaccination and some did not. No asbestos or fiber exposure was studied.
• Main results:
  • Vaccine production was feasible in 40/40 patients and vaccination in 39/40.
  • Side effects were limited to local reactions at the injection site.
  • Among the 39 evaluable patients, the disease control rate was 64.1% and the overall response rate 5.1% at 8 weeks. At 6 months they were 48.7% and 12.8%. By tumor group, Table 1 shows disease control in 25 of 39 at 8 weeks and 19 of 39 at 6 months.
  • Median overall survival from diagnosis was 43.7 months among 13 patients with glioblastoma multiforme. It was 41.9 months among 12 patients with metastatic breast cancer, measured from diagnosis of metastatic disease. It was 48.8 months among 10 patients with malignant pleural mesothelioma.
  • The comparison figures (16.0, 37.2 and 23.4 months for glioblastoma, metastatic breast cancer and mesothelioma, respectively) came from previously published studies, not from a control group in this trial.
  • In the malignant pleural mesothelioma group, median overall survival from diagnosis was 48.8 months (range 21.8 to 134.8). Measured from the first vaccination, it was 28.2 months (range 5.6 to 63.0).
  • In the mesothelioma group, disease control at 8 weeks and/or 6 months was seen in 7/10 (70%) patients, all without other treatment at those time points. This compared with 1/13 in glioblastoma and 2/12 in metastatic breast cancer.
  • Stable disease was observed at 8 weeks and/or 6 months in 24/39 patients. In 12/39 patients this occurred without any concomitant treatment.
  • Patients with stable disease at 8 weeks and disease control at 6 months had a longer median overall survival than patients without disease control at either time point (N = 34, P = 0.0356).
  • All patients with partial or complete responses also received concomitant treatment during vaccination.
  • Disease control was associated with type 1 cytokine T-cell reactivity. WT1-specific IFN-gamma-producing CD4+ T-cell responses were associated with overall survival.
  • Antigen-nonspecific type 2 CD8+ T-cell responses were common before vaccination but showed no association with clinical outcome.
• The authors' conclusion: The authors concluded that WT1-mRNA/DC vaccination is feasible, safe and immunogenic and shows clinical activity in patients with advanced solid tumors. They suggested it has the potential to help improve survival.
• Limitations the authors state:
  • The study was performed on a pre-selected group of patients, so the authors stated that further clinical studies are needed to confirm the vaccine's clinical efficacy.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Median Overall Survival.

Related studies

• Integration of the PD-L1 inhibitor atezolizumab and WT1/DC vaccination into standard-of-care first-line treatment for patients with epithelioid malignant pleural mesothelioma-Protocol of the Immuno-MESODEC study — J. Van den Bossche, M. De Laere, et al. (2024)
• Adjuvant dendritic cell based immunotherapy (DCBI) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal mesothelioma, a phase II single centre open-label clinical trial: rationale and design of the MESOPEC trial — N.L. de Boer, J.P. van Kooten, et al. (2019)
• WT1 peptide vaccinations induce CD4 and CD8 T cell immune responses in patients with mesothelioma and non-small cell lung cancer — L.M. Krug, T. Dao, et al. (2010)
• Wilms tumor 1/cytokeratin dual-color immunostaining reveals distinctive staining patterns in metastatic melanoma, metastatic carcinoma, and mesothelial cells in pleural fluids: an effective first-line test for the workup of malignant effusions — J.R. Conner, E.S. Cibas, et al. (2014)
• Anti-cancer therapy using dendritic cells and apoptotic tumour cells: pre-clinical data in human mesothelioma and acute myeloid leukaemia — M. Grégoire, C. Ligeza-Poisson, et al. (2003)
• A Prime-Boost Vaccination Approach Induces Lung Resident Memory CD8+ T Cells Derived from Central Memory T Cells That Prevent Tumor Lung Metastasis — H. Xu, M. Yue, et al. (2024)

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