Journal Article

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

Peeters, Marc, Nijs, Griet, Berneman, Zwi N., Oka, Yoshihiro, De Laere, Maxime, van Dam, Peter A., Vandenbosch, Irma, Saevels, Kirsten, Op de Beeck, Bart, Van Damme, Pierre, Sugiyama, Haruo, Huizing, Manon T., Van den Bossche, Jolien, Willemen, Yannick, De Reu, Hans, Snoeckx, Annemiek, Stein, Barbara, Llewellyn-Lacey, Sian, Cools, Nathalie, Anguille, Sébastien, Germonpré, Paul, Altintas, Sevilay, Smits, Evelien L.J.M., Van den Brande, Jan, Lammens, Martin, Oner, Gizem, Lion, Eva, Oji, Yusuke, Couttenye, Marie M., Van de Velde, Ann L., Rutsaert, Lynn, Caluwaerts, Kim, Van Tendeloo, Viggo F., Price, David A., Specenier, Pol

2025

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adjuvants / Adult / Aged / Antigens / Breast cancer / Breast Neoplasms - immunology / Breast Neoplasms - pathology / Breast Neoplasms - therapy / Cancer / Cancer immunotherapy / Cancer Research / Cancer vaccines / Cancer Vaccines - adverse effects / Cancer Vaccines - immunology / Cancer Vaccines - therapeutic use / Care and treatment / CD4 antigen / CD8 antigen / Cell therapy / Clinical outcomes / Clinical trial / Correspondence / Cytokines / Cytotoxicity / Dendritic cell vaccination / Dendritic cells / Dendritic Cells - immunology / Dendritic Cells - transplantation / Disease control / Female / Glioblastoma / Glioblastoma - immunology / Glioblastoma - therapy / Glioblastoma multiforme / Glioma / Hematology / Humans / Immunogenicity / Immunotherapy / Leukemia / Lung Neoplasms - immunology / Lung Neoplasms - therapy / Lymphocytes / Lymphocytes T / Male / Malignancy / Medical colleges / Medical prognosis / Medical research / Medicine / Medicine & Public Health / Medicine, Experimental / Mesothelioma / Mesothelioma, Malignant / Messenger RNA / Metastases / Metastasis / Middle Aged / mRNA / Oncology / Patient outcomes / Patients / Peptides / Pleural Neoplasms - immunology / Pleural Neoplasms - therapy / Proteins / Remission (Medicine) / RNA, Messenger - genetics / RNA, Messenger - immunology / Solid tumors / T cells / Th1 Cells - immunology / Toxicity / Treatment Outcome / Tumor necrosis factor-TNF / Tumors / Vaccination / Vaccines / Wilms’ tumor protein / WT1 Proteins - genetics / WT1 Proteins - immunology