ArticleProceedings of the National Academy of Sciences of the United States of America2015
Generation of MANAbodies specific to HLA-restricted epitopes encoded by somatically mutated genes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed.
- Recurrent Immunogenic Neoantigens and Their Cognate T-cell Receptors in Treatment-Resistant Metastatic Prostate Cancer.Cancer discovery · 2026Article
- Bispecific antibodies and CAR T cells targeting a TP53 mutation-associated neoantigen show discordant affinity requirements.The Journal of clinical investigation · 2026Article
- A KRASMolecular therapy. Oncology · 2025Article
- Targeting mutated KRAS by HLA-A*02:01 restricted anti-KRAS TCR-mimic CAR and bispecific T cell engager.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Neoantigen-driven personalized tumor therapy: An update from discovery to clinical application.Chinese medical journal · 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
- Identification of nonsense-mediated decay inhibitors that alter the tumor immune landscape.eLife · 2025Article
- Bispecific antibody targeting shared indel-derived neoantigen of APC.Frontiers in immunology · 2025Article
- Potent antitumor activity of a bispecific T-cell engager antibody targeting the intracellular antigen KRAS G12V.Biomolecules & biomedicine · 2024Article
- Preclinical studies show that Co-STARs combine the advantages of chimeric antigen and T cell receptors for the treatment of tumors with low antigen densities.Science translational medicine · 2024Article
- Systematic discovery of neoepitope-HLA pairs for neoantigens shared among patients and tumor types.Nature biotechnology · 2024Article
- Facts and Hopes in Immunotherapy Strategies Targeting Antigens Derived from KRAS Mutations.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Review
- Conformational plasticity of RAS Q61 family of neoepitopes results in distinct features for targeted recognition.Nature communications · 2023Article
- Neoantigens: promising targets for cancer therapy.Signal transduction and targeted therapy · 2023Review
- Cancer Immunotherapy Beyond Checkpoint Blockade:JACC. CardioOncology · 2022Review
- TCR-mimic bispecific antibodies to target the HIV-1 reservoir.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Identification of Neoantigens in Cancer Cells as Targets for Immunotherapy.International journal of molecular sciences · 2022Review
- Review
- Chimeric Antigen Receptors Directed at Mutant KRAS Exhibit an Inverse Relationship Between Functional Potency and Neoantigen Selectivity.Cancer research communications · 2022Article
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Authors and funding
12 authors.
Funding
Abstract
Mutant epitopes encoded by cancer genes are virtually always located in the interior of cells, making them invisible to conventional antibodies. We here describe an approach to identify single-chain variable fragments (scFvs) specific for mutant peptides presented on the cell surface by HLA molecules. We demonstrate that these scFvs can be successfully converted to full-length antibodies, termed MANAbodies, targeting "Mutation-Associated Neo-Antigens" bound to HLA. A phage display library representing a highly diverse array of single-chain variable fragment sequences was first designed and constructed. A competitive selection protocol was then used to identify clones specific for mutant peptides bound to predefined HLA types. In this way, we obtained two scFvs, one specific for a peptide encoded by a common KRAS mutant and the other by a common epidermal growth factor receptor (EGFR) mutant. The scFvs bound to these peptides only when the peptides were complexed with HLA-A2 (KRAS peptide) or HLA-A3 (EGFR peptide). We converted one scFv to a full-length antibody (MANAbody) and demonstrate that the MANAbody specifically reacts with mutant peptide-HLA complex even when the peptide differs by only one amino acid from the normal, WT form.
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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.