Synthetic long-peptide vaccines that present chosen neoepitopes directly, often with an adjuvant — the most clinically mature personalized-vaccine approach.
Fujian Medical University Union Hospital is recruiting for a Phase I trial of autologous peptide-induced active immunity for AML maintenance therapy. The study addresses the high recurrence rates of AML post-chemotherapy, positioning neoantigen vaccines as a lower-toxicity alternative to allogeneic transplantation for preventing relapse.
Dana-Farber Cancer Institute is conducting a Phase I trial evaluating NeoVax (personalized neoantigen peptides + poly-ICLC) combined with CDX-301 and either Nivolumab or Pembrolizumab for melanoma. The study is currently active but not recruiting, testing the combination of a personalized vaccine platform with checkpoint inhibitors and a novel adjuvant.
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.
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.
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.
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.
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.
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.
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.
A new pipeline utilizes GFP-like protein scaffolds and the mouse nidogen G2 domain for stable, soluble neoantigen display. This modular platform allows for the insertion of tumor-derived peptides without compromising structural integrity, offering a scalable method for next-generation subunit cancer vaccines.
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.
A study identifies L3EMP, a microprotein encoded by LINC00973, as a driver of lung adenocarcinoma progression via SIRT1 stabilization. The research highlights L3EMP as a potential neoantigen target, evaluating its immunotherapeutic potential using synthetic peptides and CAR-T cells.
The Jaime Leandro Foundation for Therapeutic Cancer Vaccines has launched an expanded access protocol for synthetic long peptide neoantigen vaccines in solid tumors. This intermediate patient access initiative highlights growing demand for personalized therapies outside of traditional clinical trial structures.
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.
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.
Researchers introduced HERMES, a structure-based, physics-guided machine learning model that predicts TCR interactions with peptides on MHC class I alleles. Trained on the protein universe without direct TCR-pMHC data, HERMES achieved up to 0.72 correlation with experimental data and enables de novo design of immunogenic peptides.
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.
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).
Mayo Clinic is conducting a Phase I/II trial of a personalized neoantigen peptide-based vaccine combined with pembrolizumab for advanced solid tumors. The study aims to determine safety and tolerability of the vaccine alone versus in combination with the checkpoint inhibitor, targeting specific tumor neoantigens.
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.
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.
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.
Seqker Biosciences has completed a Phase I/II trial of a personalized neoantigen peptide vaccine for advanced solid tumors. The study leveraged whole exome and RNA sequencing to identify patient-specific mutations, aiming to evaluate safety, immunogenicity, and clinical efficacy in a population with limited treatment alternatives.
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.
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.
pVACview is introduced as an interactive visualization tool designed to streamline neoantigen prioritization and selection. The tool addresses the complexity of navigating multiple prediction algorithms, transcript annotations, and peptide registers, facilitating more efficient candidate selection for downstream clinical applications.
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.