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Neoantigen × AI
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FIELD MAP / MODALITY

Peptide vaccines

Synthetic long-peptide vaccines that present chosen neoepitopes directly, often with an adjuvant — the most clinically mature personalized-vaccine approach.

Topic64 items2026-05-29 – 2026-07-13
Modalities
Peptide vaccines64TCR & T-cell receptor34mRNA vaccines31Dendritic-cell vaccines25Shared & off-the-shelf16DNA vaccines11Lipid nanoparticles5Viral-vector vaccines4Oncolytic viruses1
01
AI / Methods

DRIVE: a comprehensive resource deciphering drug-induced transcriptomic and splicing response in cancer cell.

The DRIVE database addresses the lack of resources linking drug-induced transcriptomic changes to neoantigen potential by integrating 3,911 samples across 278 drugs and 272 cell lines. Using LLMs for metadata curation, it quantifies differential splicing events and predicts resulting HLA-binding peptides. This resource enables the systematic identification of immunogenic neoantigens derived from drug-induced aberrant splicing, offering a new avenue for vaccine target discovery in pharmacotherapy contexts.

europepmc · brief 2026-07-13 · published 2026-07-10
02
AI / Methods

Geometric deep learning improves generalizability of MHC-bound peptide predictions - Nature

Researchers have identified limitations in current sequence-based approaches for predicting MHC-peptide interactions and introduced a structure-based method using geometric deep learning (GDL). By employing self-supervised learning on 3D structures without exposure to binding affinity data, the model shows improved generalizability across unseen MHC alleles. This suggests a viable path toward more robust computational tools for neoantigen identification in cancer immunotherapy.

news · brief 2026-07-12 · published 2024-12-19
04
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.

TCR & T-cell receptor
biorxiv · brief 2026-07-09 · published 2026-07-06
05
AI / Methods

AI-driven neoantigen identification: a comprehensive review from somatic variant calling to T cell recognition.

This review details AI workflows that combine transcriptomics and immunopeptidomics to nominate candidate neoepitopes, moving beyond tailored experimental methods. It emphasizes the critical challenge of predicting which tumor mutations result in T cell recognition via class I and II peptide-binding grooves. The piece serves as a technical baseline for understanding the computational layers required to reduce false positives in personalized vaccine design.

europepmc · brief 2026-07-08 · published 2026-07-06
06
Clinical

Neoantigen Peptide Vaccine Plus Pembrolizumab in Renal Cell Carcinoma

Peking University First Hospital is launching a Phase I investigator-initiated trial to evaluate a personalized neoantigen polyepitope peptide vaccine combined with pembrolizumab in advanced renal cell carcinoma. The study aims to enroll 5-8 patients across safety and expansion cohorts to address the high rate of primary or acquired resistance to pembrolizumab monotherapy.

Kidney cancer (RCC)
clinicaltrials · brief 2026-07-07 · published 2026-07-07
07
AI / Methods

Preclinical proof of concept for a personalized SNAP™-TIL (Specific Neo-Antigen Peptides-TIL) therapy platform.

Preclinical proof-of-concept data demonstrates a SNAP™-TIL platform that combines computational modeling with PepSeq screening to credential and enrich TILs for specific neoantigens. By isolating T cells with high affinity for patient-specific HLA class II proteins before expansion, the platform aims to overcome the rarity of neoantigen-reactive cells in less immunogenic tumors. The approach yielded products with 96% CD3+ content and a mix of effector and central memory subsets, suggesting improved precision in TIL manufacturing.

europepmc · brief 2026-07-06 · published 2026-07-05
08
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.

TCR & T-cell receptor
biorxiv · brief 2026-07-05 · published 2026-07-04
09
Clinical

IDH1-mutant vaccine in newly diagnosed astrocytoma: final analysis of the multicenter, single-arm, open-label, first-in-human phase 1 NOA16 trial.

The NOA16 trial provides 8-year follow-up data for an IDH1-R132H peptide vaccine in newly diagnosed astrocytoma, demonstrating sustained immunogenicity and favorable long-term outcomes. Participants with grade IV disease achieved a median overall survival of 106.1 months, significantly outperforming historical controls. Sustained antibody responses to the neoepitope correlated with favorable clinical courses, validating the target for mutant IDH1-driven cancers.

europepmc · brief 2026-07-02 · published 2026-07-01
10
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.

TCR & T-cell receptor
biorxiv · brief 2026-06-28 · published 2026-06-25
11
AI / Methods

Measuring peptide-MHC generalization to unseen alleles across both HLA classes

Researchers demonstrate that reported peptide-MHC (pMHC) AUROCs of 0.85-0.95 overstate generalization due to data leakage from dense immunopeptidome data on well-studied alleles. Using a harmonized corpus of 5.8 million measurements, they show true generalization to unseen alleles is in the high 0.7s. They released an open benchmark and a new predictor that outperforms eight existing models by +0.22 to +0.37 AUROC on least-studied genes.

biorxiv · brief 2026-06-24 · published 2026-06-23
21
Clinical

A Phase 1b/2, Multi-center, Single Arm Study to Assess the Safety and Efficacy of Neoantigen Synthetic Long Peptide Vaccines in Patients With Local Or Metastatic Solid Tumors

[ENROLLING_BY_INVITATION · PHASE1, PHASE2 · Jaime Leandro Foundation for Therapeutic Cancer Vaccines] A Phase 1b/2, Multi-center, Single Arm Study to Assess the Safety and Efficacy of Neoantigen Synthetic Long Peptide Vaccines in Patients With Local Or Metastatic Solid Tumors

clinicaltrials · brief 2026-06-13 · published 2026-01-15
22
Clinical

Personalized Cancer Vaccine (PCV) Strategy in Patients With Solid Tumors and Molecular Residual Disease

Washington University School of Medicine is recruiting for a Phase I trial evaluating synthetic long peptide personalized cancer vaccines in patients with solid tumors and molecular residual disease. The study tests the hypothesis that these vaccines can generate measurable neoantigen-specific T-cell responses capable of clearing circulating tumor DNA.

clinicaltrials · brief 2026-06-13 · published 2026-01-13
23
Clinical

COLONYVAQ™, a Quantum-Classical Guided Personalized Neoantigen Vaccine for MSS Stage III Colorectal Cancer

Biogenea Pharmaceuticals is recruiting for an early Phase I trial of COLONYVAQ-CRC, a physics-aware, quantum-classical AI-guided personalized neoantigen peptide vaccine. The study evaluates safety and tolerability when administered with standard adjuvant oxaliplatin-based chemotherapy and nivolumab in patients with completely resected stage III microsatellite-stable (MSS) colorectal cancer.

Colorectal cancer
clinicaltrials · brief 2026-06-13 · published 2026-01-09
24
Clinical

GYNORYLAQ™-VLINIVAL™: Ψ-Guided Personalized Neoantigen Peptide Vaccine for High-Risk Endometrial Cancer

Also from Biogenea, the GYNORYLAQ-VLINIVAL trial is enrolling 40 patients with high-risk or recurrent endometrial carcinoma. Participants receive GYNORYLAQ-TM, a personalized neoantigenic peptide vaccine generated by the company’s quantum-classical engine, alongside individually selected standard-of-care regimens to assess safety and T-cell immunity.

clinicaltrials · brief 2026-06-13 · published 2026-01-07
25
AI / Methods

Multi-pathway feature-level interpretability in MHC-I antigen presentation via concept-based modeling.

Researchers have introduced MHCCBM, a gray-box framework for predicting MHC-I antigen presentation that improves interpretability over black-box deep learning models. By decomposing the process into independent modules for proteasomal cleavage, TAP transport, and peptide-MHC binding, it achieves accuracy comparable to state-of-the-art predictors while allowing modular substitution of computational estimators.

europepmc · brief 2026-06-13 · published 2026-05-06
27
Clinical

Expanded Access to PCNAT-01 for Patients With Resected Pancreatic Ductal Adenocarcinoma Following Surgical Resection and Adjuvant Therapy

Anda Biopharmaceutical has launched an expanded access program for PCNAT-01, a personalized tumor neoantigen peptide vaccine, targeting patients with resected pancreatic ductal adenocarcinoma (PDAC) following adjuvant therapy. This initiative aims to reduce recurrence risk in disease-free patients who cannot participate in ongoing trials, marking a strategic move to broaden patient access outside standard clinical development pathways.

Pancreatic cancer
clinicaltrials · brief 2026-06-08 · published 2026-05-29
28
Clinical

A DNAJB1-PRKACA Fusion Kinase Peptide Vaccine Combined With Glutamine Antagonist DRP-104, Nivolumab, and Ipilimumab in Patients With Advanced Stage Fibrolamellar Carcinoma (FLC)

[NOT_YET_RECRUITING · PHASE1 · Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins] The purpose of this study is to determine whether the combination of a neoantigen vaccine targeting the DNAJB1-PRKACA fusion kinase in combination with DRP-104, Nivolumab and Ipilimumab is …

clinicaltrials · brief 2026-06-08 · published 2026-05-06
31
Clinical

Safety and Efficacy of Neoantigen-Based Personalized Immunotherapy as Consolidation Therapy After Standard Adjuvant Treatment in Resectable Stage III Colorectal Cancer or Non-Small Cell Lung Cancer

Ying Yuan has completed a phase 1 study evaluating neoantigen-based personalized immunotherapy as consolidation therapy after standard adjuvant treatment in resectable stage III colorectal cancer and NSCLC. The trial confirmed that the 300 μg/peptide dose is well-tolerated, establishing safety for future efficacy assessments.

Lung cancer (NSCLC)Colorectal cancer
clinicaltrials · brief 2026-06-08 · published 2026-03-31
33
Clinical

Personalized Neo-Antigen Peptide Vaccine for the Treatment of Stage IIIC-IV Melanoma, Hormone Receptor Positive HER2 Negative Metastatic Refractory Breast Cancer or Stage III-IV Non-Small Cell Lung Cancer

Fred Hutchinson Cancer Center is recruiting for a phase 1 trial of a personalized neo-antigen peptide vaccine combined with the Th1 polarizing adjuvant poly ICLC. The study targets stage IIIC-IV melanoma, metastatic breast cancer, and stage III-IV NSCLC to induce polyclonal cytolytic T cell immunity.

MelanomaLung cancer (NSCLC)Breast cancer
clinicaltrials · brief 2026-06-08 · published 2026-03-12
34
Clinical

Testing the Addition of an Individualized Vaccine to Durvalumab and Tremelimumab and Chemotherapy in Patients With Metastatic Triple Negative Breast Cancer

The National Cancer Institute is conducting a phase 2 trial testing the addition of a personalized synthetic long peptide neoantigen vaccine to durvalumab, tremelimumab, and chemotherapy in metastatic triple-negative breast cancer. The study compares outcomes with and without the vaccine to determine if it enhances the efficacy of the existing regimen.

Breast cancer
clinicaltrials · brief 2026-06-08 · published 2026-05-13
35
AI / Methods

Counterfactual Peptide Editing for Causal TCR--pMHC Binding Inference

A new training framework called Counterfactual Invariant Prediction (CIP) addresses shortcut learning in TCR-pMHC binding models by enforcing invariance to non-anchor peptide edits. Evaluated on VDJdb-IEDB benchmarks, CIP reduces the shortcut index by 39.7% compared to baselines, improving model robustness under family-held-out and distance-aware evaluation protocols.

TCR & T-cell receptor
arxiv · brief 2026-06-08 · published 2026-04-14
36
AI / Methods

Enhancing TCR-Peptide Interaction Prediction with Pretrained Language Models and Molecular Representations

The LANTERN framework combines large protein language models (ESM-1b) with chemical representations (MolFormer) to enhance TCR-peptide interaction prediction. It demonstrates superior performance in zero-shot and few-shot scenarios compared to existing models like ChemBERTa, leveraging robust negative sampling to address data scarcity in personalized vaccine development.

TCR & T-cell receptor
arxiv · brief 2026-06-08 · published 2025-04-22
37
AI / Methods

Learning residue-level context for modeling protein-protein interactions

ReCLIP utilizes a transformer architecture to learn interaction-specific representations at the individual residue level, addressing limitations in current protein language models that aggregate information across entire proteins. The framework demonstrates strong performance in predicting mutation-induced perturbations (AUROC = 0.973) and enables zero-shot prediction of peptide-MHC binding across unseen alleles with an AUROC up to 0.972. By identifying structurally coherent residue neighborhoods, the method links pathogenic genetic variants to interaction perturbations, offering a precise tool for analyzing neoantigen-MHC interactions.

biorxiv · brief 2026-06-06 · published 2026-06-04
40
Clinical

rHSC-DIPGVax Plus Checkpoint Blockade for the Treatment of Newly Diagnosed DIPG and DMG

Ann & Robert H Lurie Children's Hospital of Chicago is recruiting for a Phase I trial of rHSC-DIPGVax, an off-the-shelf neoantigen heat shock protein vaccine containing 16 peptides, combined with BALSTILIMAB and ZALIFRELIMAB. The trial targets newly diagnosed DIPG and DMG patients who have completed radiation, aiming to assess safety and tolerability of this non-personalized approach.

Shared & off-the-shelf
clinicaltrials · brief 2026-06-03 · published 2026-03-17
41
Clinical

DNA prime and peptide boost immunization elicits robust neoantigen-specific CD8 <sup>+</sup> T cell responses and therapeutic protection in mouse tumor models.

Preclinical data demonstrates that a DNA prime and peptide boost immunization strategy elicits robust neoantigen-specific CD8+ T-cell responses and therapeutic protection in mouse tumor models. This regimen eliminated tumors in therapeutic settings and may be enhanced by combining with anti-PD-1 antibodies, offering a potential manufacturing and efficacy optimization for future vaccine platforms.

europepmc · brief 2026-06-03 · published 2026-01-11
42
AI / Methods

HLA micropolymorphisms confine neoantigen conformational adaptability and guide T cell receptor selectivity.

Research reveals that HLA micropolymorphisms confine neoantigen conformational adaptability, directly guiding T cell receptor selectivity. Specifically, micropolymorphisms in HLA-A*03:02 versus A*03:01 prevent TCR binding by altering the neoantigen's conformational ensemble rather than peptide binding, highlighting a critical mechanistic constraint for vaccine design that must be accounted for in antigen selection pipelines.

TCR & T-cell receptor
europepmc · brief 2026-06-03 · published 2026-06-01
43
Clinical

Personalized Neo-Antigen Peptide Vaccine for the Treatment of Stage IIIC-IV Melanoma, Hormone Receptor Positive HER2 Negative Metastatic Refractory Breast Cancer or Stage III-IV Non-Small Cell Lung Cancer

Fred Hutchinson Cancer Center has launched a Phase I trial recruiting patients with stage IIIC-IV melanoma, metastatic breast cancer, or stage III-IV NSCLC. The study evaluates a personalized neo-antigen peptide vaccine combined with the Th1-polarizing adjuvant poly ICLC to induce polyclonal cytolytic T cell immunity.

MelanomaLung cancer (NSCLC)Breast cancer
clinicaltrials · brief 2026-06-02 · published 2026-03-12
44
Clinical

Testing the Addition of an Individualized Vaccine to Durvalumab and Tremelimumab and Chemotherapy in Patients With Metastatic Triple Negative Breast Cancer

The National Cancer Institute (NCI) is conducting a Phase II trial testing the addition of a personalized synthetic long peptide neoantigen vaccine to durvalumab, tremelimumab, and nab-paclitaxel in metastatic triple-negative breast cancer. This aims to determine if adding the vaccine improves outcomes over the standard chemo-immunotherapy backbone.

Breast cancer
clinicaltrials · brief 2026-06-02 · published 2026-05-13
45
Clinical

Safety & Efficacy of DC Vaccine and TMZ for the Treatment of Newly-diagnosed Glioblastoma After Surgery

Beijing Tiantan Hospital completed a Phase I study evaluating autologous dendritic cells loaded with tumor neoantigen peptides alongside temozolomide in newly diagnosed glioblastoma. The trial focused on safety and preliminary efficacy, contributing data on DC-based vaccine platforms in this indication.

Dendritic-cell vaccinesGlioblastoma
clinicaltrials · brief 2026-06-02 · published 2026-05-04
46
Clinical

Trial of a Personalized and Adaptive Neoantigen Dose-Adjusted Vaccine Concurrently With Pembrolizumab

UNC Lineberger Comprehensive Cancer Center has suspended a Phase I trial of the PANDA-VAC personalized neoantigen peptide vaccine administered concurrently with pembrolizumab. The study was designed for advanced squamous NSCLC and head and neck squamous cell carcinoma, assessing safety and dose adjustment protocols.

Lung cancer (NSCLC)Head & neck cancer
clinicaltrials · brief 2026-06-02 · published 2026-04-23
48
AI / Methods

Vaccination with cationic liposome-encapsulated CD4 and CD8 T cell neoepitopes induces superior tumor control.

Preclinical data demonstrates that cationic liposome-encapsulated CD4 and CD8 T cell neoepitopes induce superior tumor control in a murine colorectal cancer model. The liposomal formulation significantly enhanced neoepitope-specific T cell responses compared to soluble peptides, curing 60% of mice with lethal tumors.

Colorectal cancer
europepmc · brief 2026-06-02 · published 2026-04-05
51
Clinical

Personalized Cancer Vaccine (PCV) Strategy in Patients With Solid Tumors and Molecular Residual Disease

Washington University School of Medicine is recruiting for a Phase 1 trial evaluating synthetic long peptide personalized cancer vaccines in solid tumors with molecular residual disease. The study tests the hypothesis that these vaccines, co-administered with poly-ICLC, can generate neoantigen-specific T-cell responses sufficient to clear circulating tumor DNA.

clinicaltrials · brief 2026-05-31 · published 2026-01-13
52
Clinical

GYNORYLAQ™-VLINIVAL™: Ψ-Guided Personalized Neoantigen Peptide Vaccine for High-Risk Endometrial Cancer

Biogenea is enrolling patients in a Phase I trial for GYNORYLAQ-VLINIVAL, a quantum-classical engine-generated personalized neoantigen vaccine for high-risk endometrial cancer. The study evaluates the safety and feasibility of manufacturing GMP-grade vaccines in a real-world therapeutic context, with secondary objectives focusing on T-cell immunity characterization.

clinicaltrials · brief 2026-05-31 · published 2026-01-07
54
Clinical

Neoantigen Vaccines in Pancreatic Cancer in the Window Prior to Surgery

A completed Phase 1 randomized trial by Washington University School of Medicine evaluated optimized synthetic long peptide (SLP) neoantigen vaccines co-administered with poly-ICLC in pancreatic cancer patients. The study compared vaccine administration following neoadjuvant chemotherapy and surgery versus a window prior to surgery, aiming to assess safety and immunogenicity in the perioperative setting.

Pancreatic cancer
clinicaltrials · brief 2026-05-30 · published 2026-05-06
55
Clinical

A DNAJB1-PRKACA Fusion Kinase Peptide Vaccine Combined With Glutamine Antagonist DRP-104, Nivolumab, and Ipilimumab in Patients With Advanced Stage Fibrolamellar Carcinoma (FLC)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins has launched a Phase 1 trial for a DNAJB1-PRKACA fusion kinase peptide vaccine in advanced fibrolamellar carcinoma. The study tests the safety and antitumor activity of this neoantigen vaccine combined with the glutamine antagonist DRP-104, nivolumab, and ipilimumab, with primary endpoints including objective response rate (ORR).

clinicaltrials · brief 2026-05-30 · published 2026-05-06
57
Clinical

A Vaccine (Neoantigen-Targeted ppDC) for the Treatment of H3 G34-mutant Diffuse Hemispheric Glioma

Jonsson Comprehensive Cancer Center is running a Phase I trial for a neoantigen-targeted peptide-pulsed dendritic cell (ppDC) vaccine in patients with H3 G34-mutant diffuse hemispheric glioma. The active, non-recruiting study focuses on identifying the best dose and safety profile of this patient-specific immunotherapy.

Dendritic-cell vaccinesGlioblastoma
clinicaltrials · brief 2026-05-30 · published 2026-02-17
58
AI / Methods

DapPep: Domain Adaptive Peptide-agnostic Learning for Universal T-cell Receptor-antigen Binding Affinity Prediction

Researchers introduced DapPep, a domain-adaptive peptide-agnostic learning framework for universal TCR-antigen binding affinity prediction. Using a lightweight self-attention architecture combined with protein language models, DapPep outperforms existing tools in predicting binding for unseen peptides, addressing a key bottleneck in neoantigen vaccine design for data-scarce settings.

TCR & T-cell receptor
arxiv · brief 2026-05-30 · published 2024-11-26
59
AI / Methods

Physicochemically Informed Dual-Conditioned Generative Model of T-Cell Receptor Variable Regions for Cellular Therapy

PhysicoGPTCR, a dual-conditioned generative protein Transformer, is introduced for designing TCR variable regions. Trained on TCR-peptide-HLA triples with physicochemical descriptors, the model improves binding-competent clone generation and sequence space exploration compared to baselines like GPTCR and VAEs, advancing computer-aided cellular therapy.

TCR & T-cell receptor
arxiv · brief 2026-05-30 · published 2025-10-07
61
Clinical

A Phase 1b/2, Multi-center, Single Arm Study to Assess the Safety and Efficacy of Neoantigen Synthetic Long Peptide Vaccines in Patients With Local Or Metastatic Solid Tumors

The Jaime Leandro Foundation for Therapeutic Cancer Vaccines is conducting a Phase 1b/2 multi-center study of synthetic long peptide neoantigen vaccines. The trial is currently enrolling by invitation to assess safety and efficacy in patients with local or metastatic solid tumors.

clinicaltrials · brief 2026-05-29 · published 2026-01-15
62
Clinical

Expanded Access to PCNAT-01 for Patients With Resected Pancreatic Ductal Adenocarcinoma Following Surgical Resection and Adjuvant Therapy

Anda Biopharmaceutical has opened an expanded access program for PCNAT-01, a personalized tumor neoantigen peptide vaccine, for patients with resected pancreatic ductal adenocarcinoma. The program targets disease-free patients post-surgery and adjuvant therapy to reduce recurrence risk, subject to regulatory and sponsor review.

Pancreatic cancer
clinicaltrials · brief 2026-05-29 · published 2026-05-29
64
AI / Methods

Neoantigen-based T cell vaccines design strategies, therapeutic barriers, and clinical advances.

A comprehensive review in EuropePMC synthesizes the current state of neoantigen-based T cell vaccines, covering design strategies, therapeutic barriers, and clinical advances. The article examines mechanisms across mRNA, peptide, and dendritic cell platforms, highlighting synergies with checkpoint blockade and the challenges of immunosuppressive tumor microenvironments.

mRNA vaccinesDendritic-cell vaccines
europepmc · brief 2026-05-29 · published 2026-05-01
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