ArticleCancer immunology, immunotherapy : CII2023
Dual targeting ovarian cancer by Muc16 CAR T cells secreting a bispecific T cell engager antibody for an intracellular tumor antigen WT1.
Article in Cancer immunology, immunotherapy : CII, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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27 citing papers in PubMed, 31 citations in OpenAlex.
- Breast and Contralateral Axillary Lymph Node Metastases After Ovarian Cancer Surgery: A Case Report.Clinical case reports · 2026Article
- Targeted cellular micropharmacies deliver therapeutic agents to the brain.EMBO molecular medicine · 2026Article
- Human CD3 complex is required for the generation of T-cell receptor-like chimeric antigen receptor targeting WT1 in natural killer cells.Cancer immunology, immunotherapy : CII · 2026Article
- MUC4-targeted CAR-T Cells Restrain Chemotherapy-resistant Colorectal Cancer.bioRxiv : the preprint server for biology · 2026Article
- Nanobodies targeting the Epstein-Barr virus EBNA1 DNA binding domain inhibit tumor growth.Journal of nanobiotechnology · 2026Article
- Trispecific targeting of T cells engineered with TCR mimic antibodies to limit antigen escape.Journal for immunotherapy of cancer · 2026Article
- Advancing adoptive T cell therapy in ovarian cancer: barriers, innovations, and emerging platforms.Journal for immunotherapy of cancer · 2026Review
- Advances in adoptive cell therapy for ovarian cancer.Frontiers in immunology · 2026Review
- Engineering CAR-T cells for solid tumors: overcoming antigenic, trafficking, and microenvironmental barriers.Frontiers in immunology · 2026Review
- Next-generation CAR-T cells design: leveraging tumor features for enhanced efficacy.Molecular cancer · 2025Review
- WT1 gene: a potential therapeutic target for multiple cancer treatment strategies.Clinical and experimental medicine · 2025Review
- Challenges and limitations of chimeric antigen receptor T-cell therapies in solid tumors: why are approvals restricted to hematologic malignancies?Journal of hematology & oncology · 2025Review
- Challenges and perspectives of CAR-T cell therapy in solid tumours: insights from gastric cancer.British journal of cancer · 2025Review
- Dual targeting of solid tumors using cytokine-induced killer cells modified with a CAR anti-tenascin C and a secretable EGFRxCD3 bispecific antibody.Cancer immunology, immunotherapy : CII · 2025Article
- Advances and obstacles of T cell-based immunotherapy in gynecological malignancies.Molecular cancer · 2025Review
- Immune evasion in ovarian cancer: implications for immunotherapy and emerging treatments.Trends in immunology · 2025Review
- Current strategies for armoring chimeric antigen receptor T-cells to overcome barriers of the solid tumor microenvironment.Frontiers in immunology · 2025Review
- Role of Immunotherapy in Ovarian Cancer: Advances, Challenges, and Future Perspectives.Cancer treatment and research · 2025Review
- From molecular design to clinical translation: dual-targeted CAR-T strategies in cancer immunotherapy.International journal of biological sciences · 2025Review
- Armoring chimeric antigen receptor (CAR) T cells as micropharmacies for cancer therapy.Immuno-oncology technology · 2024Review
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Epithelial ovarian cancer is the most lethal of gynecological cancers. The therapeutic efficacy of chimeric antigen receptor (CAR) T cell directed against single antigens is limited by the heterogeneous target antigen expression in epithelial ovarian tumors. To overcome this limitation, we describe an engineered cell with both dual targeting and orthogonal cytotoxic modalities directed against two tumor antigens that are highly expressed on ovarian cancer cells: cell surface Muc16 and intracellular WT1. Muc16-specific CAR T cells (4H11) were engineered to secrete a bispecific T cell engager (BiTE) constructed from a TCR mimic antibody (ESK1) reactive with the WT1-derived epitope RMFPNAPYL (RMF) presented by HLA-A2 molecules. The secreted ESK1 BiTE recruited and redirected other T cells to WT1 on the tumor cells. We show that ESK1 BiTE-secreting 4H11 CAR T cells exhibited enhanced anticancer activity against cancer cells with low Muc16 expression, compared to 4H11 CAR T cells alone, both in vitro and in mouse tumor models. Dual orthogonal cytotoxic modalities with different specificities targeting both surface and intracellular tumor-associated antigens present a promising strategy to overcome resistance to CAR T cell therapy in epithelial ovarian cancer and other cancers.
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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.