{
  "abstract": "Background Development of personalized therapeutic cancer vaccines has been accelerated by lowered sequencing costs, highly efficient production processes and encouraging immunogenicity results from Phase I/II clinical trials. An optimal personalized vaccine approach should elicit poly- and tumor-specific immune responses, resulting in clinically significant disease control. Empirical data supporting associations between criteria applied for neoantigen selection pipelines and their immunogenic potential in vivo are however scarce.Methods Here we analyzed parameters embedded in our proprietary NeoSELECT platform including baseline molecular data derived from multiomics RNA- and exome-sequencing, against the neoantigen-specific immunogenicity data from the Phase I/II VB N-01 and Phase I VB N-02 trials. Data from 33 and 13 patients, respectively, was analyzed originating from mostly heavily pretreated patients with 12 different cancer diagnoses.Results NeoSELECT successfully identified neoantigens eliciting T-cell responses in patients treated with the individualized VB10.NEO vaccine. In the N-01 and N-02 trials, 94% and 100% of patients, respectively, demonstrated a neoantigen-specific T-cell response, with 45% (286/634) and 58% (136/234) of all selected neoantigens (up to 20 neoantigens encoded per patient) showing immunogenicity by in vitro stimulated (IVS) ELISpot. Epitopes that were immunogenic at baseline and continued to be stably immunogenic or amplified (greater than 1.3-fold increase) in on-treatment samples were significantly enriched for high-quality epitopes, defined by predicted MHC class I and II binding affinity, clonality and expression as detected on the RNA and circulating free DNA level. This indicates that the criteria applied by NeoSELECT are important for selecting neoantigens presented by the individual patient’s tumor cells, which is a requirement to induce clinical responses. Although the patient cohort was highly heterogeneous, a positive association between high-quality immunogenic neoantigens and overall survival was observed for patients in the N-01 trial.Conclusions In summary, these results demonstrate that the individualized VB10.NEO vaccine, and the NeoSELECT platform, selects and targets neoantigens that elicit robust immune responses that may contribute to clinical anti-tumor efficacy and improved patient survival.Acknowledgements We would like to thank the patients and their families, the N-01 and N-02 investigators and staff for their participation in the trials. Atezolizumab was supplied by Roche for the N-02 trial.Trial Registration The clinical trials have the following ClinicalTrials.gov identifiers: NCT03548467 (N-01) and NCT05018273 (N-02).Ethics Approval The study protocols and their amendments were approved by local or national ethics committees for each participating site before study initiation. The studies were done in accordance with the ICH GCP guidelines, Declaration of Helsinki and all applicable laws, and all patients provided written informed consent.",
  "authors": [
    {
      "affiliations": [
        "Nykode Therapeutics, Oslo, Norway"
      ],
      "name": "Miriam Aure"
    },
    {
      "affiliations": [
        "Nykode Therapeutics, Oslo, Norway"
      ],
      "name": "Andreas Midbøe Hoff"
    },
    {
      "affiliations": [
        "Nykode Therapeutics, Oslo, Norway"
      ],
      "name": "Kaja Christine Graue Berg"
    },
    {
      "affiliations": [
        "Nykode Therapeutics, Oslo, Norway"
      ],
      "name": "Ingvild Sørum Leikfoss"
    },
    {
      "affiliations": [
        "Nykode Therapeutics, Oslo, Norway"
      ],
      "name": "Hariz Iskandar Bin Hassan"
    },
    {
      "affiliations": [
        "Charité University of Medicine Berlin Comprehensive Cancer Center, Berlin, Germany"
      ],
      "name": "Sebastian Ochsenreither"
    },
    {
      "affiliations": [
        "Nykode Therapeutics, Oslo, Norway"
      ],
      "name": "Agnete Brunsvik Fredriksen"
    }
  ],
  "title": "117 Integrative analyses of multiomics data and biomarker readout demonstrate clinical and immunological relevance of individualized vaccine design via the NeoSELECT™ platform",
  "uid": "ec3c49fa-3844-5441-8c82-abc617914fce"
}