ArticleNature medicine2022
Immunogenicity and therapeutic targeting of a public neoantigen derived from mutated PIK3CA.
Article in Nature medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.
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Who cites it
102 citing papers in PubMed, 120 citations in OpenAlex.
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- HLA micropolymorphisms confine neoantigen conformational adaptability and guide T cell receptor selectivity.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Hallmarks and correlates of effective adoptive cell immunotherapy for cancer.Nature reviews. Immunology · 2026Review
- FOXM1-Specific TCR-Engineered T Cells Target Non-Small Cell Lung Cancer.Cancer immunology research · 2026Article
- PRECISE-seq reveals disease-relevant TCR repertoires with phenotypic plasticity.The Journal of experimental medicine · 2026Article
- Article
- Identification of MHC Ligands Through Allele-Guided Isolation Combined With Machine Learning for Improved MHC Assignment Using ARDisplay-I.Molecular & cellular proteomics : MCP · 2026Article
- Neoantigen Targeting as a Novel Approach for Therapy-Resistant Tumors.Molecular diagnosis & therapy · 2026Review
- T cell receptor-engineered T cells targeting the TP53R248Q neoantigen elicit antitumor effects in human cancer models.The Journal of clinical investigation · 2026Article
- Dynamic Allostery in T Cell Receptor Specificity: A Role for Peptides and MHC Polymorphisms in Allosterically Tuning Immune Recognition.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- Pipe dream to pipeline: Journey of cancer vaccines and the road ahead.Cell reports. Medicine · 2026Review
- HIV- and cytomegalovirus-specific human memory CD8+ T cells are activated and expanded independent of co-stimulatory signaling by T-cell receptor-specific immunotherapeutics.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- A panel of four autoantibodies to tumour-associated antigens in patients with prostate cancer and its potential for multi-cancer detection.British journal of cancer · 2026Article
- Palmitic acid-triggered B7H3 palmitoylation promotes immune escape.Nature communications · 2026Article
- Systematic evaluation of neoepitope predictions challenges clinically observed T-cell responses and their impact on immune evasion.Journal for immunotherapy of cancer · 2026Article
- Adoptive T Cell therapy for cancer and autoimmune disease: current advances, challenges, and future directions.Oncology reviews · 2026Article
- Bioinformatics-based screening and prediction of compounds and antigen epitopes for immune targets with point mutations in colitis-associated colorectal cancer.Discover oncology · 2025Article
- Circulating T-cell receptor repertoire and clinicopathological correlations in breast cancer patients: immune repertoire analysis from the VGH-TAYLOR study.Breast cancer research : BCR · 2025Article
42 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 3 institutions in 1 country.
Funding
Abstract
Public neoantigens (NeoAgs) represent an elite class of shared cancer-specific epitopes derived from recurrently mutated driver genes. Here we describe a high-throughput platform combining single-cell transcriptomic and T cell receptor (TCR) sequencing to establish whether mutant PIK3CA, among the most frequently genomically altered driver oncogenes, generates an immunogenic public NeoAg. Using this strategy, we developed a panel of TCRs that recognize an endogenously processed neopeptide encompassing a common PIK3CA hotspot mutation restricted by the prevalent human leukocyte antigen (HLA)-A*03:01 allele. Mechanistically, immunogenicity to this public NeoAg arises from enhanced neopeptide/HLA complex stability caused by a preferred HLA anchor substitution. Structural studies indicated that the HLA-bound neopeptide presents a comparatively 'featureless' surface dominated by the peptide's backbone. To bind this epitope with high specificity and affinity, we discovered that a lead TCR clinical candidate engages the neopeptide through an extended interface facilitated by an unusually long CDR3β loop. In patients with diverse malignancies, we observed NeoAg clonal conservation and spontaneous immunogenicity to the neoepitope. Finally, adoptive transfer of TCR-engineered T cells led to tumor regression in vivo in mice bearing PIK3CA-mutant tumors but not wild-type PIK3CA tumors. Together, these findings establish the immunogenicity and therapeutic potential of a mutant PIK3CA-derived public NeoAg.
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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.