ArticleBlood2025
CD70 CAR T cells secreting an anti-CD33/anti-CD3 dual-targeting antibody overcome antigen heterogeneity in AML.
Article in Blood, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Preclinical advances and mechanistic insights of CAR-T therapy for acute myeloid leukemia: from target iteration to microenvironment regulation.Annals of medicine · 2026Review
- Comparative clinical outcomes and single-cell profiling of CD19 CAR-T versus blinatumomab for relapsed/refractory B-ALL.Journal for immunotherapy of cancer · 2026Article
- Pediatric AML CAR T cell therapy.Molecular therapy. Oncology · 2026Review
- Precision Oncology in Thymic Epithelial Tumors: Therapeutic Horizons and Implementation Barriers.International journal of molecular sciences · 2026Review
- The search for safe and effective CAR-T targets in AML.Blood cancer journal · 2026Review
- T cell-engaging bispecific antibodies for myeloid malignancies: Targets, formats, and clinical challenges.Cell reports. Medicine · 2026Review
- CD84 is a specific target for acute myeloid leukemia CAR-T cell therapy.Nature communications · 2026Article
- Genome Agnostic Reprogramming of Acute Myelocytic Leukemia Hallmarks by Targeting Non-Oncogene Addictions with Azacitidine Plus Pioglitazone and All-Trans Retinoic Acid.International journal of molecular sciences · 2026Review
- Advancing adoptive T cell therapy in ovarian cancer: barriers, innovations, and emerging platforms.Journal for immunotherapy of cancer · 2026Review
- Immunological and pathological roles of Siglecs: a molecular review.Frontiers in immunology · 2026Review
- Advances in T cell-based immunotherapy for osteosarcoma.Frontiers in immunology · 2026Review
- From monoclonals to bispecific T cell engagers: the evolving antibody-based therapy landscape in acute myeloid leukemia.Frontiers in immunology · 2026Review
- Pandora's Box of AML: HowBiomedicines · 2025Review
- Review
- ROR2-specific CAR T cells are effective against hematologic and solid tumors and well tolerated in mice.Cell reports. Medicine · 2025Article
- Strategic innovations: Tackling challenges of immunotherapy in acute myeloid leukemia.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2025Article
- CAR-T cell therapy for cancer: current challenges and future directions.Signal transduction and targeted therapy · 2025Review
- CD70: An emerging target for integrated cancer diagnosis and therapy.Clinical and translational medicine · 2025Review
- CD22 CAR-T cells secreting CD19 T-cell engagers for improved control of B-cell acute lymphoblastic leukemia progression.Journal for immunotherapy of cancer · 2025Article
- Emerging Role of Chimeric Antigen Receptor-Natural Killer Cells for the Treatment of Hematologic Malignancies.Cancers · 2025Review
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Abstract
abstractCD70 has emerged as a promising target in acute myeloid leukemia (AML), and we have previously demonstrated the potency of an optimized CD70-targeted ligand-based chimeric antigen receptor (CAR). However, here, we identify in vivo CD70 antigen escape as a limitation of single-antigen targeting. Combination targeting of CD70 and CD33 may overcome AML antigen heterogeneity. We hypothesized that modifying our CD70 CAR platform to secrete a bispecific T-cell engaging antibody molecule (TEAM) targeting CD33 (7033) would create a therapeutic window whereby AML heterogeneity could be addressed without increasing tissue toxicity. We found that CD33 TEAMs mediated specific cytotoxicity across AML cell lines, including CD33 or CD70 single-antigen knockout tumors. 7033 CAR T cells eradicated tumor in an in vivo mixed tumor model of CD70 antigen escape and outperformed the previously optimized CD70 CAR in a patient-derived xenograft. In vivo gene expression profiling of CAR T cells revealed enhanced 7033 CAR T-cell pathway scoring for persistence, activation, and T-cell receptor signaling. Additionally, CD33 TEAMs successfully redirected T cells isolated from patients with AML to activate, secrete cytokines, and kill tumor targets despite exposure to substantial prior cytotoxic therapies. In summary, our findings demonstrate the feasibility of our 7033 CAR to overcome AML heterogeneity and leverage the bystander T cells of patients; this approach warrants further study in patients with this dire clinical need.
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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.