ArticleCancer immunology research2015
The nonsignaling extracellular spacer domain of chimeric antigen receptors is decisive for in vivo antitumor activity.
Article in Cancer immunology research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 367 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
367 citing papers in PubMed, 2 syntheses or guidelines pooled it, 514 citations in OpenAlex.
- Mapping the clinical landscape of multifunctional CAR T cells: Targets, trends, and synergies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Pooled it
- The synergistic immunotherapeutic impact of engineered CAR-T cells with PD-1 blockade in lymphomas and solid tumors: a systematic review.Frontiers in immunology · 2024Pooled it
- Fine-tuning affinity and spacer design enhances T cell potency in DLL3 and BCMA CAR T cells.mAbs · 2026Article
- Development of chimeric antigen receptors targeting the γδ T cell receptor.Molecular therapy. Oncology · 2026Article
- Double activation and low IL-2 manufacturing protocol increase expansion of healthy and patient-derived CAR-Tregs.Molecular therapy. Advances · 2026Article
- Mechanisms, optimization strategies, and salvage options for CAR-T cell therapy.Biomarker research · 2026Review
- Novel PSCA-Targeting Adapter Molecules for Late-Stage RevCAR-T Cell Therapy in Prostate Cancer.International journal of molecular sciences · 2026Article
- Review
- Review
- Immunotherapy in acute myeloid leukemia: The antibodies, TriKEs, and CARs on the arduous road to cure.Blood reviews · 2026Review
- Single-cell genomics links targeted functional manipulations to efficacy-associated chromatin signatures in CAR T cells.Research square · 2026Article
- A Review of Recent Advances in Chimeric Antigen Receptor (CAR) T-Cell Therapy for Hepatocellular Carcinoma.Medical science monitor : international medical journal of experimental and clinical research · 2026Review
- Precise control of switchable chimeric antigen receptor T cells allows enhanced safety and less T cell exhaustion.Journal of translational medicine · 2026Article
- Humanized and Charge-Optimized CSPG4-Specific CAR-T Cells show Enhanced Efficacy against Head and Neck Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Innovative biomaterial solutions for enhancing the efficacy of tumor immunotherapy.Immunologic research · 2026Review
- NOT-gated chimeric antigen receptor circuits in T and NK cells.Cell systems · 2026Article
- CAR-T cell therapy in breast cancer management: expanding horizon and overcoming challenges beyond hematologic cancers.Molecular biology reports · 2026Review
- 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
- Modulating AP-1 enables CAR T cells to establish an intratumoral stemlike reservoir and overcomes resistance to PD-1 blockade.Science immunology · 2026Article
- Targeting urological cancers with CAR-T cell therapy: current landscape and future directions.Journal of translational medicine · 2026Review
307 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
8 authors at 2 institutions in 1 country.
Funding
Abstract
The use of synthetic chimeric antigen receptors (CAR) to redirect T cells to recognize tumor provides a powerful new approach to cancer immunotherapy; however, the attributes of CARs that ensure optimal in vivo tumor recognition remain to be defined. Here, we analyze the influence of length and composition of IgG-derived extracellular spacer domains on the function of CARs. Our studies demonstrate that CD19-CARs with a long spacer from IgG4 hinge-CH2-CH3 are functional in vitro but lack antitumor activity in vivo due to interaction between the Fc domain within the spacer and the Fc receptor-bearing myeloid cells, leading to activation-induced T-cell death. We demonstrate that in vivo persistence and antitumor effects of CAR-T cells with a long spacer can be restored by modifying distinct regions in the CH2 domain that are essential for Fc receptor binding. Our studies demonstrate that modifications that abrogate binding to Fc receptors are crucial for CARs in which a long spacer is obligatory for tumor recognition as shown here for a ROR1-specific CAR. These results demonstrate that the length and composition of the extracellular spacer domain that lacks intrinsic signaling function can be decisive in the design of CARs for optimal in vivo activity.
Indexed as
Identifiers
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.