ArticleHuman vaccines & immunotherapeutics2017
Pre-clinical development of gene modification of haematopoietic stem cells with chimeric antigen receptors for cancer immunotherapy.
Article in Human vaccines & immunotherapeutics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 32 citations in OpenAlex.
- Cytokine-Engineered Chimeric Antigen Receptor-T Cell Therapy: How to Balance the Efficacy and Toxicity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Domain-substituted IGF2 tag modulates targeting of lentiviral gene therapy for Hunter syndrome.EMBO molecular medicine · 2025Article
- Gene-edited hematopoietic stem cells for leukemia and lymphoma treatment: a systematic review of preclinical and translational evidence.Discover oncology · 2025Review
- Human cancer-targeted immunity via transgenic hematopoietic stem cell progeny.Nature communications · 2025Article
- Article
- Understanding Autoimmunity: Mechanisms, Predisposing Factors, and Cytokine Therapies.International journal of molecular sciences · 2024Review
- CAR products from novel sources: a new avenue for the breakthrough in cancer immunotherapy.Frontiers in immunology · 2024Review
- 5-HTInternational journal of molecular sciences · 2023Article
- Targeting advanced prostate cancer with STEAP1 chimeric antigen receptor T cell and tumor-localized IL-12 immunotherapy.Nature communications · 2023Article
- Emerging approaches for preventing cytokine release syndrome in CAR-T cell therapy.Journal of materials chemistry. B · 2022Review
- Advances in modular control of CAR-T therapy with adapter-mediated CARs.Advanced drug delivery reviews · 2022Review
- Humanized Mice Are Precious Tools for Preclinical Evaluation of CAR T and CAR NK Cell Therapies.Cancers · 2020Review
- Review
- CARs: Beyond T Cells and T Cell-Derived Signaling Domains.International journal of molecular sciences · 2020Review
- DCLK1 Monoclonal Antibody-Based CAR-T Cells as a Novel Treatment Strategy against Human Colorectal Cancers.Cancers · 2019Article
- Development of Hematopoietic Stem Cell-Engineered Invariant Natural Killer T Cell Therapy for Cancer.Cell stem cell · 2019Article
- Anti-CAR-engineered T cells for epitope-based elimination of autologous CAR T cells.Cancer immunology, immunotherapy : CII · 2019Article
- Applications of molecular engineering in T-cell-based immunotherapies.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · 2019Review
- A Cetuximab-Mediated Suicide System in Chimeric Antigen Receptor-Modified Hematopoietic Stem Cells for Cancer Therapy.Human gene therapy · 2019Article
- IND-Enabling Studies for a Clinical Trial to Genetically Program a Persistent Cancer-Targeted Immune System.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Patients with refractory or recurrent B-lineage hematologic malignancies have less than 50% of chance of cure despite intensive therapy and innovative approaches are needed. We hypothesize that gene modification of haematopoietic stem cells (HSC) with an anti-CD19 chimeric antigen receptor (CAR) will produce a multi-lineage, persistent immunotherapy against B-lineage malignancies that can be controlled by the HSVsr39TK suicide gene. High-titer third-generation self-inactivating lentiviral constructs were developed to deliver a second-generation CD19-specific CAR and the herpes simplex virus thymidine kinase HSVsr39TK to provide a suicide gene to allow ablation of gene-modified cells if necessary. Human HSC were transduced with such lentiviral vectors and evaluated for function of both CAR and HSVsr39TK. Satisfactory transduction efficiency was achieved; the addition of the suicide gene did not impair CAR expression or antigen-specific cytotoxicity, and determined marked cytotoxicity to ganciclovir. NSG mice transplanted with gene-modified human HSC showed CAR expression not significantly different between transduced cells with or without HSVsr39TK, and expression of anti-CD19 CAR conferred anti-tumor survival advantage. Treatment with ganciclovir led to significant ablation of gene-modified cells in mouse tissues. Haematopoietic stem cell transplantation is frequently part of the standard of care for patients with relapsed and refractory B cell malignancies; following HSC collection, a portion of the cells could be modified to express the CD19-specific CAR and give rise to a persistent, multi-cell lineage, HLA-independent immunotherapy, enhancing the graft-versus-malignancy activity.
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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.