ArticleThe Journal of clinical investigation2017
A therapeutic T cell receptor mimic antibody targets tumor-associated PRAME peptide/HLA-I antigens.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 59 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
59 citing papers in PubMed, 92 citations in OpenAlex.
- Multi-dimensional orchestration of binders for improved CAR-T immunotherapy.Cancer letters · 2026Review
- Targeting the C/EBPβ-PRAME-EZH2 complex modulates the Netrin-4/AKT axis to inhibit renal cancer tumorigenesis and metastasis.Cell death and differentiation · 2026Article
- A generalizable system for antigenic peptide targeting across HLA-I allotypes.bioRxiv : the preprint server for biology · 2026Article
- The role of immunoproteasome in diabetes and diabetes-related complications.Genes & diseases · 2026Review
- Shared PRAME epitopes are T-cell targets in NUT carcinoma.Journal for immunotherapy of cancer · 2026Article
- Trispecific targeting of T cells engineered with TCR mimic antibodies to limit antigen escape.Journal for immunotherapy of cancer · 2026Article
- Article
- Therapeutic Opportunities in Melanoma Through PRAME Expression.Biomedicines · 2025Review
- Development of an innovative approach for early diagnosis of cervical cancer using TCR‑like antibodies targeting HPV18 E6 and E7 peptides.Molecular medicine reports · 2025Article
- De novo design and structure of a peptide-centric TCR mimic binding module.Science (New York, N.Y.) · 2025Article
- Effect of HLA restriction on racial and ethnic disparities in access to immune therapies for advanced synovial sarcoma.The oncologist · 2025Article
- Therapeutic Targeting and Structural Characterization of a Sotorasib-Modified KRAS G12C-MHC I Complex Demonstrate the Antitumor Efficacy of Hapten-Based Strategies.Cancer research · 2025Article
- The Future of TCR-like Antibodies in Diagnosis and Potential Application Targets.Current molecular medicine · 2025Review
- Bispecific antibody targeting shared indel-derived neoantigen of APC.Frontiers in immunology · 2025Article
- Design of high specificity binders for peptide-MHC-I complexes.bioRxiv : the preprint server for biology · 2024Article
- Review
- Potent antitumor activity of a bispecific T-cell engager antibody targeting the intracellular antigen KRAS G12V.Biomolecules & biomedicine · 2024Article
- T Cell-Engaging Bispecific Antibodies Targeting gp100 and PRAME: Expanding Application from Uveal Melanoma to Cutaneous Melanoma.Pharmaceutics · 2024Review
- Targeting PRAME for acute myeloid leukemia therapy.Frontiers in immunology · 2024Review
- PRAME Expression: A Target for Cancer Immunotherapy and a Prognostic Factor in Uveal Melanoma.Investigative ophthalmology & visual science · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
Preferentially expressed antigen in melanoma (PRAME) is a cancer-testis antigen that is expressed in many cancers and leukemias. In healthy tissue, PRAME expression is limited to the testes and ovaries, making it a highly attractive cancer target. PRAME is an intracellular protein that cannot currently be drugged. After proteasomal processing, the PRAME300-309 peptide ALYVDSLFFL (ALY) is presented in the context of human leukocyte antigen HLA-A*02:01 molecules for recognition by the T cell receptor (TCR) of cytotoxic T cells. Here, we have described Pr20, a TCR mimic (TCRm) human IgG1 antibody that recognizes the cell-surface ALY peptide/HLA-A2 complex. Pr20 is an immunological tool and potential therapeutic agent. Pr20 bound to PRAME+HLA-A2+ cancers. An afucosylated Fc form (Pr20M) directed antibody-dependent cellular cytotoxicity against PRAME+HLA-A2+ leukemia cells and was therapeutically effective against mouse xenograft models of human leukemia. In some tumors, Pr20 binding markedly increased upon IFN-γ treatment, mediated by induction of the immunoproteasome catalytic subunit β5i. The immunoproteasome reduced internal destructive cleavages within the ALY epitope compared with the constitutive proteasome. The data provide rationale for developing TCRm antibodies as therapeutic agents for cancer, offer mechanistic insight on proteasomal regulation of tumor-associated peptide/HLA antigen complexes, and yield possible therapeutic solutions to target antigens with ultra-low surface presentation.
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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.