ArticleScience translational medicine2013
Identification of a Titin-derived HLA-A1-presented peptide as a cross-reactive target for engineered MAGE A3-directed T cells.
Article in Science translational medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 457 papers, 1 of them a synthesis 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
457 citing papers in PubMed, 1 synthesis or guideline pooled it, 661 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
- Article
- The evolution of cellular therapies in sarcoma: Breakthroughs, challenges, and future directions.Human vaccines & immunotherapeutics · 2026Review
- Receptor-defined targeting of a genomically unique melanoma-enriched noncanonical antigen.Signal transduction and targeted therapy · 2026Article
- What Does the Shape Space of T Cell Epitopes Look Like?Immunological reviews · 2026Review
- Chimeric antigen receptor T cell therapy cardiotoxicity: a narrative review.Cardio-oncology (London, England) · 2026Review
- Breathing new life into T-cell receptor-engineered T-cell therapy in solid tumors: enhancing strategies to expand the universality of precision therapy.Experimental hematology & oncology · 2026Review
- Comprehensive mapping of identical sequences across human proteins emphasizes the widespread issue of shared epitopes in self-antigens.NAR genomics and bioinformatics · 2026Article
- The evolution of display technologies for antibody drug discovery.Trends in biotechnology · 2026Review
- T cell adaptation in chronic infections and tumors.Cellular & molecular immunology · 2026Review
- Generation of T cells with reduced off-target cross-reactivities by engineering co-signalling receptors.Nature biomedical engineering · 2026Article
- Overcoming T cell tolerance to tumor self-antigens through catch-bond engineering.Science (New York, N.Y.) · 2026Article
- KRASScience advances · 2026Article
- Functional Genomics Illuminates Mechanisms of Anthracycline Cardiotoxicity.JACC. CardioOncology · 2026Article
- Safety and biologic activity of a bispecific T cell receptor targeting HIV Gag in males living with HIV: a first-in-human trial.Nature communications · 2026Article
- Optimally engineered HLA/peptide-specific CAR-T cells outperform TCR-T cells to eradicate solid tumors.Science advances · 2026Article
- Trispecific targeting of T cells engineered with TCR mimic antibodies to limit antigen escape.Journal for immunotherapy of cancer · 2026Article
- CD8 co-receptor modulates the specificity profile of the 1G4 TCR against NY-ESO-1.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Translational strategy to support the first-in-human study of a TCR-like T cell bispecific with anFrontiers in immunology · 2026Article
- Beyond Hyperglycemia: The Role of Sodium-Glucose Cotransporter 2 Inhibitors in Cancer Treatment-related Cardiac Dysfunction.US cardiology · 2026Review
397 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
30 authors at 2 institutions in 1 country.
Funding
Abstract
MAGE A3, which belongs to the family of cancer-testis antigens, is an attractive target for adoptive therapy given its reactivation in various tumors and limited expression in normal tissues. We developed an affinity-enhanced T cell receptor (TCR) directed to a human leukocyte antigen (HLA)-A*01-restricted MAGE A3 antigen (EVDPIGHLY) for use in adoptive therapy. Extensive preclinical investigations revealed no off-target antigen recognition concerns; nonetheless, administration to patients of T cells expressing the affinity-enhanced MAGE A3 TCR resulted in a serious adverse event (SAE) and fatal toxicity against cardiac tissue. We present a description of the preclinical in vitro functional analysis of the MAGE A3 TCR, which failed to reveal any evidence of off-target activity, and a full analysis of the post-SAE in vitro investigations, which reveal cross-recognition of an off-target peptide. Using an amino acid scanning approach, a peptide from the muscle protein Titin (ESDPIVAQY) was identified as an alternative target for the MAGE A3 TCR and the most likely cause of in vivo toxicity. These results demonstrate that affinity-enhanced TCRs have considerable effector functions in vivo and highlight the potential safety concerns for TCR-engineered T cells. Strategies such as peptide scanning and the use of more complex cell cultures are recommended in preclinical studies to mitigate the risk of off-target toxicity in future clinical investigations.
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.