{
  "abstract": "Background Immunotherapies utilizing patient-derived tumor neoepitopes have begun to gain attention in the field of oncology as promising targets to advance personalized cancer treatments. However, there are many barriers to therapeutic development of neoepitope-based therapies, including challenges with their selection, immunogenicity and a lack of modular treatment platforms for incorporation of neoepitope target peptides. Previously developed artificial antigen presenting cells (aAPC’s) comprised of iron dextran-based nanoparticles conjugated with peptide-MHC complexes and anti-CD28 antibodies, were optimized as a platform and advanced for clinical use at NexImmune for the activation and expansion of multi-antigen-specific cytotoxic T cell therapies. Together we aim to apply this, modular aAPC platform to optimize identification of neoepitopes and expansion of tumor-neoepitope specific patient-derived T cells.Methods Tumor sequencing was obtained for a stage IV lung cancer patient and used to identify a panel of 26 candidate HLA-A24-restricted neoepitopes. These peptides were screened on aAPCs using three independent healthy donor T cells, resulting in immunogenicity data that was used to choose a cocktail of 5 neoepitopes. This peptide cocktail was loaded onto aAPCs and used to enrich and expand patient-derived CD8+ T cells the 5 separate neoepitope specific T cells simultaneously. Resultant cultures were analyzed via flow cytometry, sorted, and sequenced to analyze the T cell receptor (TCR) repertoire and genomic expression.Results Herein, we demonstrate a workflow for selecting patient-specific neoepitopes and applying them to aAPC’s for expansion of patient-neoepitope specific CD8+ T cells. We successfully expanded 4/5 of the chosen neoepitopes including a P53-neoepitope specific mutation from patient derived PBMC. Single cell sequencing data on P53-expanded T cells revealed patterns of clonal dominance and correlated T cell clones expressed genes with proliferation and effector function.Conclusions These results indicate that healthy donor responses may be used to predict neoantigen immunogenicity in patients and demonstrates that aAPC platforms can be translated for neoantigen-specific expansion of human CD8+ T cells. Future work will include investigating the effector function of expanded patient T cells through cytokine release and peptide-pulsed lymphoblastoid cell line killing assays. This novel neoantigen-based aAPC platform has the potential to transform both the screening of therapeutic targets and expansion of functional T cells to advance the future of personalized cancer immunotherapy.Ethics Approval This study was approved by Johns Hopkins University’s Institutional Ethics Review Board, Parent ID: NA_00027947, Number: CIR00001668.",
  "authors": [
    {
      "affiliations": [
        "Johns Hopkins University, Baltimore, MD, USA"
      ],
      "name": "Emily Ariail"
    },
    {
      "affiliations": [
        "NexImmune Inc., Gaithersburg, MD, USA"
      ],
      "name": "Sojung Kim"
    },
    {
      "affiliations": [
        "NexImmune Inc., Gaithersburg, MD, USA"
      ],
      "name": "Lauren Suarez"
    },
    {
      "affiliations": [
        "Johns Hopkins University, Baltimore, MD, USA"
      ],
      "name": "Shweta Singh"
    },
    {
      "affiliations": [
        "NexImmune Inc., Gaithersburg, MD, USA"
      ],
      "name": "Kristi Jones"
    },
    {
      "affiliations": [
        "NexImmune Inc., Gaithersburg, MD, USA"
      ],
      "name": "Mathias Oelke"
    },
    {
      "affiliations": [
        "Johns Hopkins University, Baltimore, MD, USA"
      ],
      "name": "Jonathan P Schneck"
    }
  ],
  "title": "998 Identification and expansion of neoantigen-specific patient T cells using artificial antigen presenting cells, aAPC",
  "uid": "ecf015f3-3132-5952-80fc-962b79ccceef"
}