ArticleJournal for immunotherapy of cancer2022
WT1-specific TCRs directed against newly identified peptides install antitumor reactivity against acute myeloid leukemia and ovarian carcinoma.
Article in Journal for immunotherapy of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 23 citations in OpenAlex.
- WT1 peptide vaccines of post-allogeneic HSCT maintenance immunotherapy for pediatric acute leukemias: a phase 2 study.Blood advances · 2026Trial
- Advances and prospects in cell therapy for cancer: explorations from T cells to stem cells.Signal transduction and targeted therapy · 2026Review
- Innovative combinatory approaches with dendritic cell-based vaccines: bridging preclinical insights and clinical challenges.Clinical and experimental medicine · 2026Review
- Article
- Trispecific targeting of T cells engineered with TCR mimic antibodies to limit antigen escape.Journal for immunotherapy of cancer · 2026Article
- Predicting antigen-specific T-cell immunity against Wilms tumor 1 in hematologic cancer.Leukemia · 2025Article
- WT1 gene: a potential therapeutic target for multiple cancer treatment strategies.Clinical and experimental medicine · 2025Review
- Current developments in T-cell receptor therapy for acute myeloid leukemia.Blood advances · 2025Review
- DNA barcoded peptide-MHC multimers to measure and monitor minor histocompatibility antigen-specific T cells after allogeneic stem cell transplantation.Journal for immunotherapy of cancer · 2024Article
- Immune Shielding of Human Heart Valves: A Proof-of-Concept Study of HLA-Targeting Therapy for Transplantations.JACC. Basic to translational science · 2024Article
- Targeting epigenetic regulation and post-translational modification with 5-Aza-2' deoxycytidine and SUMO E1 inhibition augments T-cell receptor therapy.Journal for immunotherapy of cancer · 2024Article
- Article
- T-Cell Mediated Immune Rejection of Beta-2-Microglobulin Knockout Induced Pluripotent Stem Cell-Derived Kidney Organoids.Stem cells translational medicine · 2024Article
- Antibody-mediated delivery of viral epitopes to redirect EBV-specific CD8Cancer gene therapy · 2024Article
- New Horizons in Immunology and Immunotherapy of Acute Leukemias and Related Disorders.Cancers · 2023Article
- Direct identification of T cell epitopes in cancer tissues.Annals of pancreatic cancer · 2023Article
- A library of cancer testis specific T cell receptors for T cell receptor gene therapy.Molecular therapy oncolytics · 2023Article
- Human iPSC-derived preclinical models to identify toxicity of tumor-specific T cells with clinical potential.Molecular therapy. Methods & clinical development · 2023Article
- Evolution by innovation as a driving force to improve TCR-T therapies.Frontiers in oncology · 2023Review
- PRAME and CTCFL-reactive TCRs for the treatment of ovarian cancer.Frontiers in immunology · 2023Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTranscription factor Wilms' tumor gene 1 (WT1) is an ideal tumor target based on its expression in a wide range of tumors, low-level expression in normal tissues and promoting role in cancer progression. In clinical trials, WT1 is targeted using peptide-based or dendritic cell-based vaccines and T-cell receptor (TCR)-based therapies. Antitumor reactivities were reported, but T-cell reactivity is hampered by self-tolerance to WT1 and limited number of WT1 peptides, which were thus far selected based on HLA peptide binding algorithms.
methodsIn this study, we have overcome both limitations by searching in the allogeneic T-cell repertoire of healthy donors for high-avidity WT1-specific T cells, specific for WT1 peptides derived from the HLA class I associated ligandome of primary leukemia and ovarian carcinoma samples.
resultsUsing broad panels of malignant cells and healthy cell subsets, T-cell clones were selected that demonstrated potent and specific anti-WT1 T-cell reactivity against five of the eight newly identified WT1 peptides. Notably, T-cell clones for WT1 peptides previously used in clinical trials lacked reactivity against tumor cells, suggesting limited processing and presentation of these peptides. The TCR sequences of four T-cell clones were analyzed and TCR gene transfer into CD8+ T cells installed antitumor reactivity against WT1-expressing solid tumor cell lines, primary acute myeloid leukemia (AML) blasts, and ovarian carcinoma patient samples.
conclusionsOur approach resulted in a set of naturally expressed WT1 peptides and four TCRs that are promising candidates for TCR gene transfer strategies in patients with WT1-expressing tumors, including AML and ovarian carcinoma.
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