ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014
Therapeutic efficacy of an Fc-enhanced TCR-like antibody to the intracellular WT1 oncoprotein.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 49 citations in OpenAlex.
- Article
- Neoantigen-driven personalized tumor therapy: An update from discovery to clinical application.Chinese medical journal · 2025Review
- Immune-infiltrated kidney organoid-on-chip model for assessing T cell bispecific antibodies.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Facile repurposing of peptide-MHC-restricted antibodies for cancer immunotherapy.Nature biotechnology · 2023Article
- Review
- Conformation-selective rather than avidity-based binding to tumor associated antigen derived peptide-MHC enables targeting of WT1-pMHC low expressing cancer cells by anti-WT1-pMHC/CD3 T cell engagers.Frontiers in immunology · 2023Article
- Validation and promise of a TCR mimic antibody for cancer immunotherapy of hepatocellular carcinoma.Scientific reports · 2022Article
- Emerging new therapeutic antibody derivatives for cancer treatment.Signal transduction and targeted therapy · 2022Review
- TCR mimic compounds for pHLA targeting with high potency modalities in oncology.Frontiers in oncology · 2022Review
- Targeting intracellular WT1 in AML with a novel RMF-peptide-MHC-specific T-cell bispecific antibody.Blood · 2021Article
- T-Cell Receptor Mimic Antibodies for Cancer Immunotherapy.Molecular cancer therapeutics · 2021Review
- Phase I dose escalation safety and feasibility study of autologous WT1-sensitized T cells for the treatment of patients with recurrent ovarian cancer.Journal for immunotherapy of cancer · 2021Article
- Intracellular targeting of STIP1 inhibits human cancer cell line growth.Translational cancer research · 2021Article
- Immune escape and immunotherapy of acute myeloid leukemia.The Journal of clinical investigation · 2020Review
- Empirical and Rational Design of T Cell Receptor-Based Immunotherapies.Frontiers in immunology · 2020Review
- ALK and RET Inhibitors Promote HLA Class I Antigen Presentation and Unmask New Antigens within the Tumor Immunopeptidome.Cancer immunology research · 2019Article
- The Antitumor Activity of TCR-Mimic Antibody-Drug Conjugates (TCRm-ADCs) Targeting the Intracellular Wilms Tumor 1 (WT1) Oncoprotein.International journal of molecular sciences · 2019Article
- Targeting the MHC Ligandome by Use of TCR-Like Antibodies.Antibodies (Basel, Switzerland) · 2019Review
- Opportunities and Challenges for Antibodies against Intracellular Antigens.Theranostics · 2019Review
- T-cell receptor mimic (TCRm) antibody therapeutics against intracellular proteins.Antibody therapeutics · 2019Review
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
purposeRMFPNAPYL (RMF), a Wilms' tumor gene 1 (WT1)-derived CD8 T-cell epitope presented by HLA-A*02:01, is a validated target for T-cell-based immunotherapy. We previously reported ESK1, a high avidity (Kd < 0.2 nmol/L), fully-human monoclonal antibody (mAb) specific for the WT1 RMF peptide/HLA-A*02:01 complex, which selectively bound and killed WT1(+) and HLA-A*02:01(+) leukemia and solid tumor cell lines. EXPERIMENTAL
designWe engineered a second-generation mAb, ESKM, to have enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) function due to altered Fc glycosylation. ESKM was compared with native ESK1 in binding assays, in vitro ADCC assays, and mesothelioma and leukemia therapeutic models and pharmacokinetic studies in mice. ESKM toxicity was assessed in HLA-A*02:01(+) transgenic mice.
resultsESK antibodies mediated ADCC against hematopoietic and solid tumor cells at concentrations below 1 μg/mL, but ESKM was about 5- to 10-fold more potent in vitro against multiple cancer cell lines. ESKM was more potent in vivo against JMN mesothelioma, and effective against SET2 AML and fresh ALL xenografts. ESKM had a shortened half-life (4.9 days vs. 6.5 days), but an identical biodistribution pattern in C57BL/6J mice. At therapeutic doses of ESKM, there was no difference in half-life or biodistribution in HLA-A*02:01(+) transgenic mice compared with the parent strain. Importantly, therapeutic doses of ESKM in these mice caused no depletion of total WBCs or hematopoetic stem cells, or pathologic tissue damage.
conclusionsThe data provide proof of concept that an Fc-enhanced mAb can improve efficacy against a low-density, tumor-specific, peptide/MHC target, and support further development of this mAb against an important intracellular oncogenic protein.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.