neoag
Neoantigen × AI
Daily research signal
TOPICS / MODALITY

TCR & T-cell receptor

T-cell-receptor biology and TCR-engineered cell therapy directed at tumor neoantigens — the readout side of antigen recognition.

Topic14 items2026-06-26 – 2026-08-30
Modalities
mRNA vaccines60Peptide vaccines21TCR & T-cell receptor14Dendritic-cell vaccines12Shared & off-the-shelf8Lipid nanoparticles7DNA vaccines4Viral-vector vaccines1
01
AI / Methods

Label Noise Limits TCR-pMHC Specificity Prediction: Improved Performance Through AlphaFold3-Based Structural Modeling and Data Denoising

The study argues that label noise in TCR-pMHC specificity datasets is a major driver of weak performance for unseen peptide prediction, where structural modeling has so far shown the most predictive power. Using an AlphaFold3-based pipeline adapted for TCR-pMHC structural modeling, the authors report state-of-the-art specificity prediction that outperforms AlphaFold2.3-based and sequence-based methods and performs at par with the leading Immrep2025 competition submission. A cluster-based denoising step that removes mislabeled points from a large specificity dataset increased binder ranking accuracy by more than 70% relative to the full dataset, implying that data quality improvements could materially affect TCR-based immunotherapy and vaccine design.

Peptide vaccines
biorxiv · brief 2026-08-30 · published 2026-08-28
03
Clinical

Identification of pre-existing ubiquitous neoantigen-reactive tumor-infiltrating T-cells in a patient with metastatic pancreatic neuroendocrine tumor

A preprint investigates whether ubiquitous neoantigens—mutations shared across all metastatic sites—can overcome inter-site heterogeneity in pancreatic neuroendocrine tumors. Using whole-exome and RNA sequencing on 14 samples from a treatment-naive patient, researchers identified ubiquitous mutations and validated immunogenicity via IFN-gamma ELISpot and single-cell TCR sequencing. This approach targets durable immune responses by focusing on neoantigens present in both primary and metastatic lesions.

Pancreatic cancer
biorxiv · brief 2026-08-07 · published 2026-08-04
04
AI / Methods

Engineering antigen-driven co-stimulation and T helper cell activity into TCR-T cells with CD8-41BB fusion receptors enhances anti-tumor activity

Researchers engineered TCR-T cells with CD8-41BB fusion receptors to overcome the lack of co-stimulation and helper activity typical in TCR therapies. While wild-type CD8beta promoted CD4+ T cell activity, it failed to drive durable responses against WT1 in mouse models, suggesting further optimization is needed for high-affinity targets.

biorxiv · brief 2026-07-29 · published 2026-07-28
05
Clinical

Intermediate-size IND for Treatment of Patients With Advanced Cancer Using T Cells Engineered to Express TCR Targeting Mutant KRAS

Providence Health & Services is operating an expanded access program (NCT07614048) for T-cells engineered to express TCRs targeting mutant KRAS-G12D. The intermediate-size IND treats advanced pancreatic and colorectal cancers in patients with specific HLA types. This provides real-world data on the feasibility of manufacturing and administering KRAS-targeted adoptive cell therapy outside of traditional trial structures.

Shared & off-the-shelfPancreatic cancerColorectal cancer
clinicaltrials · brief 2026-07-25 · published 2026-07-23
07
AI / Methods

Spatial Compartmentalization of TCR Repertoires Between Primary Melanomas and Sentinel Lymph Nodes Reveals Distinct Clonal Architectures and Shared Antigen Recognition

Primary tumors and their sentinel lymph nodes are functionally linked sites of anti-tumor immunity, yet how T cell receptor (TCR) repertoires are organized across these compartments remains incompletely understood. We thus performed TCR{beta} sequencing on paired primary melanoma…

Shared & off-the-shelfMelanoma
biorxiv · brief 2026-07-11 · published 2026-07-08
08
AI / Methods

IgGM2: An All-Atom Foundation Model for Adaptive Immune Receptor Design

IgGM2 is a new all-atom foundation model for adaptive immune receptor design that jointly generates CDR residue identities and full-atom structures. Unlike modular pipelines, it uses a structure-to-design strategy to allow framework geometry to adapt to designed CDRs without separate inverse folding. This unified approach aims to improve accuracy in modeling the coupled variation of sequence, conformation, and binding geometry for antibodies and TCRs.

biorxiv · brief 2026-07-10 · published 2026-07-09
09
AI / Methods

Benchmarking AlphaFold and related deep learning approaches for modeling antibody and TCR antigen recognition

Researchers benchmarked AlphaFold2, AlphaFold3, and related deep learning methods for modeling antibody-protein, antibody-peptide, and TCR-pMHC recognition. Results indicate that increased sampling and AlphaFold3 generally outperform default AlphaFold2 settings, though predictive accuracy varies significantly by interface class. The authors note that antibody-peptide complexes remain particularly difficult to model accurately and propose model pooling as a potential solution to leverage method complementarity.

Peptide vaccines
biorxiv · brief 2026-07-09 · published 2026-07-06
10
AI / Methods

TCR-FramePose: a local-frame representation for decomposing global docking and CDR3 loop geometry in TCR-pMHC recognition

Researchers have introduced TCR-FramePose, a local-frame representation method that decomposes TCR-pMHC docking geometry into reach, offset, and orientation coordinates. Applied to 378 crystal structures, the tool captures CDR3 loop geometry and affinity-associated information beyond conventional descriptors, potentially improving the computational prediction of T cell receptor recognition.

biorxiv · brief 2026-07-07 · published 2026-07-04
11
AI / Methods

PRISM : Peptide-specificity annotation of T-cell receptors with uncertainty quantification

PRISM is a metric-learning framework that embeds TCR beta sequences into a peptide-organized latent space to predict pMHC ligands. By using structure-guided synthetic receptors to counter viral bias in training data, it abstains on out-of-distribution inputs via uncertainty modeling. Benchmarks show PRISM matches or exceeds existing models, particularly for rare epitopes.

Peptide vaccines
biorxiv · brief 2026-07-05 · published 2026-07-04
13
Clinical

Specific killing of Ewing sarcoma by TCR-T cells targeting public neogene-encoded antigens

Researchers identified neogenes (Ew_NGs) induced by the EWSR1::FLI1 fusion in Ewing sarcoma, which present peptides on HLA-I complexes. CD8+ T cells specific to these public antigens killed EwS cells in an HLA-I restricted manner, a process dependent on both the fusion and the neogene expression. Transduced TCR-T cells replicated this cytotoxicity in vivo without off-target or allogeneic activation, suggesting a viable cell therapy for relapsed/resistant cases.

Peptide vaccines
biorxiv · brief 2026-06-28 · published 2026-06-25
14
AI / Methods

replicateFest: An R Package and Shiny App for Analysis of T Cell Receptor Repertoire Data from the Functional Expansion

The replicateFest R package and Shiny app provide a framework for analyzing T cell receptor repertoire data from Functional Expansion of Specific T (FEST) assays, specifically addressing variability from biological and technical replicates. By applying negative binomial modeling to replicate experiments, it identifies clonotypes significantly expanded in antigen-stimulated conditions with adjusted p-values. This tool aims to improve reproducibility in detecting neoantigen-specific T cell responses, a critical step for guiding vaccine development and assessing checkpoint blockade efficacy.

biorxiv · brief 2026-06-26 · published 2026-06-23
Where nextAll topicsToday’s briefTrials tracker