ArticleMolecular therapy : the journal of the American Society of Gene Therapy2017
Tumor Antigen and Receptor Densities Regulate Efficacy of a Chimeric Antigen Receptor Targeting Anaplastic Lymphoma Kinase.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 259 papers, 3 of them syntheses that pooled it.
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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
259 citing papers in PubMed, 3 syntheses or guidelines pooled it, 374 citations in OpenAlex.
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- Long-term response to autologous anti-CD19 chimeric antigen receptor T cells in relapsed or refractory B cell acute lymphoblastic leukemia: a systematic review and meta-analysis.Cancer gene therapy · 2023Pooled it
- Current status and challenges of immunotherapy in ALK rearranged NSCLC.Frontiers in oncology · 2022Pooled it
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- Antibody-lectin chimeras for glyco-immune checkpoint blockade.Nature biotechnology · 2026Article
- Co-expression of non-signaling CARs enhances EGFRvIII-specific CAR T-cell cytotoxicity against head and neck squamous cell carcinoma.BMC cancer · 2026Article
- Pediatric AML CAR T cell therapy.Molecular therapy. Oncology · 2026Review
- From Delivery to Design: Site-Specific Genome Engineering for Next-Generation CAR T-Cell Therapy.Biomedicines · 2026Review
- Redifferentiation-enabled TSHRCART cells overcome antigen loss in aggressive thyroid cancers.Molecular cancer · 2026Article
- Model-dependent GD2 upregulation in Ewing sarcoma with the EZH2 inhibitor tazemetostat: Prerequisites for combination with GD2-specific CAR T cells.Research square · 2026Article
- Anti-CAR Immunity Drives Acquired Therapeutic Resistance to GD2-CAR T Cell Therapy in Diffuse Midline Glioma.medRxiv : the preprint server for health sciences · 2026Article
- αvβ3 CAR-T Cells Simultaneously Targeting Tumor and Metastases Produce Highly Effective Control in Preclinical Models of Melanoma and Triple-Negative Breast Cancer.Molecular cancer therapeutics · 2026Article
- Review
- Cell-autonomous control of CAR signaling and receptor shedding via ADAM17-mediated proteolysis.Cell · 2026Article
- Bispecific CAR T and CAR NK cells in dual-threat immunotherapy: opportunities and challenges.Molecular biology reports · 2026Review
- Bridging biomaterials and immunotherapy: hydrogel strategies for next-generation CAR-T cell treatment.Stem cell research & therapy · 2026Review
- Auto-inducible expression of chimeric antigen receptor T cells using the NR4A1 promoter.Immunology and cell biology · 2026Article
- Rational redesign of antigen binding domain improves in vivo efficacy of the CD22-CAR.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Directed evolution-based discovery of ligands for in vivo restimulation of chimeric antigen receptor T cells.Nature biomedical engineering · 2026Article
199 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
We explored the utility of targeting anaplastic lymphoma kinase (ALK), a cell surface receptor overexpressed on pediatric solid tumors, using chimeric antigen receptor (CAR)-based immunotherapy. T cells expressing a CAR incorporating the single-chain variable fragment sequence of the ALK48 mAb linked to a 4-1BB-CD3ζ signaling domain lysed ALK-expressing tumor lines and produced interferon-gamma upon antigen stimulation but had limited anti-tumor efficacy in two xenograft models of human neuroblastoma. Further exploration demonstrated that cytokine production was highly dependent upon ALK target density and that target density of ALK on neuroblastoma cell lines was insufficient for maximal activation of CAR T cells. In addition, ALK CAR T cells demonstrated rapid and complete antigen-induced loss of receptor from the T cell surface via internalization. Using a model that simultaneously modulated antigen density and CAR expression, we demonstrated that CAR functionality is regulated by target antigen and CAR density and that low expression of either contributes to limited anti-tumor efficacy of the ALK CAR. These data suggest that stoichiometric relationships between CAR receptors and target antigens may significantly impact the anti-tumor efficacy of CAR T cells and that manipulation of these parameters could allow precise tuning of CAR T cell activity.
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What OpenQuestion holds
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.