ArticleJournal of immunology (Baltimore, Md. : 1950)2009
A herceptin-based chimeric antigen receptor with modified signaling domains leads to enhanced survival of transduced T lymphocytes and antitumor activity.
Article in Journal of immunology (Baltimore, Md. : 1950), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 189 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
189 citing papers in PubMed, 293 citations in OpenAlex.
- T cells targeting carcinoembryonic antigen can mediate regression of metastatic colorectal cancer but induce severe transient colitis.Molecular therapy : the journal of the American Society of Gene Therapy · 2011Trial
- Fine-tuning affinity and spacer design enhances T cell potency in DLL3 and BCMA CAR T cells.mAbs · 2026Article
- Reduced CCL/Be-specific CD4+ T cells in CCL3-deficient or peptide-MHCII CAR-T cell-treated mice.JCI insight · 2026Article
- Optimization of a parallel CAR for B-cell lymphoma via ITAM attenuation and target specificity validation.Clinical and experimental immunology · 2026Article
- Put the CAR-T before the HRS: Advances in Anti-CD30 Immunotherapy Targeting Hodgkin/Reed-Sternberg Cells in Classical Hodgkin Lymphoma.Oncology research · 2026Review
- Control of breast cancer patient-derived xenografts by CD70-targeted HIT-CAR T cells.Frontiers in immunology · 2026Article
- Preclinical development and selection of nanobody-based CAR-T cells targeting HER2-positive solid tumors.Molecular therapy. Oncology · 2025Article
- Prospect of chimeric antigen receptor T-cell therapy for cancer.Molecular biology reports · 2025Review
- Preclinical efficacy of multi-targeting mRNA-based CAR T cell therapy in resection models of glioblastoma.Molecular therapy. Nucleic acids · 2025Article
- From TCR fundamental research to innovative chimeric antigen receptor design.Nature reviews. Immunology · 2025Review
- Enhancing the treatment potential of IL-17 antagonism in lupus nephritis: finding the right partner.Frontiers in immunology · 2025Review
- Advances in CAR optimization strategies based on CD28.Frontiers in immunology · 2025Review
- Solid tumor immunotherapy using NKG2D-based adaptor CAR T cells.Cell reports. Medicine · 2024Article
- Article
- CD5 deletion enhances the antitumor activity of adoptive T cell therapies.Science immunology · 2024Article
- The BTLA-HVEM axis restricts CAR T cell efficacy in cancer.Nature immunology · 2024Article
- Extracellular domains of CARs reprogramme T cell metabolism without antigen stimulation.Nature metabolism · 2024Article
- CAR-T-Cell-Based Cancer Immunotherapies: Potentials, Limitations, and Future Prospects.Journal of clinical medicine · 2024Review
- Induction of immortal-like and functional CAR T cells by defined factors.The Journal of experimental medicine · 2024Article
- Mechanical force determines chimeric antigen receptor microclustering and signaling.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
129 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
10 authors at 3 institutions in 2 countries.
Funding
Abstract
To generate chimeric Ag receptors (CARs) for the adoptive immunotherapy of cancer patients with ErbB2-expressing tumors, a single-chain Ab derived from the humanized mAb 4D5 Herceptin (trastuzumab) was initially linked to T cell signaling domains derived from CD28 and the CD3zeta to generate a CAR against ErbB2. Human PBLs expressing the 4D5 CAR demonstrated Ag-specific activities against ErbB2(+) tumors. However, a gradual loss of transgene expression was noted for PBLs transduced with this 4D5 CAR. When the CD3zeta signaling domain of the CAR was truncated or mutated, loss of CAR expression was not observed, suggesting that the CD3zeta signaling caused the transgene decrease, which was supported by the finding that T cells expressing 4D5 CARs with CD3zeta ITAM mutations were less prone to apoptosis. By adding 4-1BB cytoplasmic domains to the CD28-CD3zeta signaling moieties, we found increased transgene persistence in 4D5 CAR-transduced PBLs. Furthermore, constructs with 4-1BB sequences demonstrated increased cytokine secretion and lytic activity in 4D5 CAR-transduced T cells. More importantly, PBLs expressing this new version of the 4D5 CAR could not only efficiently lyse the autologous fresh tumor digests, but they could strongly suppress tumor growth in a xenogenic mouse model.
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.