1. 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.
- Author
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Berneman ZN, De Laere M, Germonpré P, Huizing MT, Willemen Y, Lion E, De Reu H, Van den Bossche J, Van den Brande J, Specenier P, Altintas S, van Dam PA, Cools N, Nijs G, Stein B, Caluwaerts K, Snoeckx A, Op de Beeck B, Saevels K, Rutsaert L, Vandenbosch I, Oner G, Lammens M, Van Damme P, Llewellyn-Lacey S, Price DA, Oka Y, Oji Y, Sugiyama H, Couttenye MM, Van de Velde AL, Van Tendeloo VF, Peeters M, Anguille S, and Smits ELJM
- Subjects
- Humans, Female, Middle Aged, Aged, Male, Adult, Mesothelioma immunology, Mesothelioma therapy, Mesothelioma, Malignant immunology, Treatment Outcome, Lung Neoplasms immunology, Lung Neoplasms therapy, Pleural Neoplasms immunology, Pleural Neoplasms therapy, Dendritic Cells immunology, WT1 Proteins immunology, Cancer Vaccines therapeutic use, Cancer Vaccines administration & dosage, Cancer Vaccines immunology, Breast Neoplasms immunology, Breast Neoplasms therapy, Breast Neoplasms pathology, Glioblastoma immunology, Glioblastoma therapy, Glioblastoma genetics, Glioblastoma pathology, RNA, Messenger genetics
- 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., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Ethics Committee of the Antwerp University Hospital/University of Antwerp (EC 10/40/266) and the Belgian Federal Agency for Medicines and Health Products (FAGG 08 − 0005) and registered at ClinicalTrials.gov (NCT01291420) and EudraCT (2011-000547-24). The sponsor’s protocol code was CCRG 11 − 001. All participants provided informed written consent in accordance with the principles of the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: VFVT and ZNB are coinventors of a now-elapsed patent covering the messenger RNA electroporation technique (Improved Transfection of Eukaryotic Cells with Linear Polynucleotides by Electroporation, WO/2003/000907)., (© 2025. The Author(s).)- Published
- 2025
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