{
  "abstract": "Malignant gliomas are treatment-resistant brain tumors needing new therapies. Virotherapy is an experimental therapy that uses attenuated viruses that conditionally replicate and lyse tumor cells and induce tumor immune therapeutic activity. How oncolytic viruses coordinate different arms of the adaptive immune response and mediate glioma therapeutic efficacy remains incompletely defined. We previously showed that an oncolytic virus expressing a shared tumor antigen, ephrin type-A receptor 2 (EphA2), created EphA2-reactive CD8+ T cell formation. Here, we show that, in addition to this CD8+ response, EphA2-oncolytic herpes simplex virus (oHSV) (C170) elicits a coordinated CD4+ T cell and B cell response with functional capacity contributing to glioma control. C170 promotes a T helper type 1 (Th1) and IL-21+CD4+ T cell population, dendritic cell (DC) activation, and germinal center B cell expansion in the tumor draining lymph nodes and produces activated B cell glioma infiltrates with enhanced antigen-presenting capacity. Depletion studies show that C170 therapeutic activity requires CD4+ T cells and that their loss reduces EphA2-specific antibody production. C170-treated mouse serum has improved complement-dependent cytotoxicity in vitro and can suppress tumor growth in vivo. These findings show that antigen-expressing oncolytic virotherapy induces a CD4+ T cell-dependent tumor therapeutic effect and generates a functional tumor antigen-specific humoral response, providing another potential mechanism contributing to C170 therapeutic efficacy.",
  "abstract_shown": true,
  "affiliations": [
    "Center for Childhood Cancer Research, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43215, USA",
    "Medical Scientist Training Program, The Ohio State University College of Medicine, Columbus, OH 43210, USA",
    "Biomedical Sciences Graduate Program, The Ohio State University College of Medicine, Columbus, OH 43210, USA",
    "Division of Hematology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA",
    "Department of Microbial Infection and Immunity, The Ohio State University College of Medicine, Columbus, OH 43210, USA",
    "Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43210, USA",
    "Department of Pediatrics, Division of Pediatric Infectious Diseases, Nationwide Children’s Hospital, Columbus, OH 43205, USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Ilse Hernandez-Aguirre"
    },
    {
      "affs": [
        0
      ],
      "name": "Doyeon Kim"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Jack Hedberg"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Alexia K. Martin"
    },
    {
      "affs": [
        0
      ],
      "name": "Yeaseul Kim"
    },
    {
      "affs": [
        0
      ],
      "name": "Phillip Perez"
    },
    {
      "affs": [
        3
      ],
      "name": "Gregory Behbehani"
    },
    {
      "affs": [
        4
      ],
      "name": "Gang Xin"
    },
    {
      "affs": [
        0,
        5,
        6
      ],
      "name": "Kevin A. Cassady"
    },
    {
      "affs": [
        0
      ],
      "name": "Ravi Dhital"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8s9pjt3yhkbtt.bib",
  "cited_by": 0,
  "doi": "10.1016/j.omton.2026.201353",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13737427/",
  "id": "8s9pjt3yhkbtt",
  "issns": [
    "2950-3299"
  ],
  "landing_url": "https://doi.org/10.1016/j.omton.2026.201353",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Article"
    ],
    [
      "openalex",
      "2403|Immunotherapy and Immune Responses"
    ]
  ],
  "openalex": "W7214791397",
  "pdf_url": null,
  "pmcid": "PMC13737427",
  "pmid": "42992029",
  "published": "2026-09-29",
  "publisher": "American Society of Gene & Cell Therapy",
  "ris": "https://research.draconitic.com/paper/8s9pjt3yhkbtt.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:22:37Z",
      "native_id": "PMC13737427",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.omton.2026.201353"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Immunotherapy and Immune Responses",
      "subfield": "immunology"
    }
  ],
  "title": "CD4+ T cells are required for tumor antigen-expressing oHSV glioma therapeutic effect and antigen-specific antibody production",
  "title_text": "CD4+ T cells are required for tumor antigen-expressing oHSV glioma therapeutic effect and antigen-specific antibody production",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:22:37Z",
  "url": "https://research.draconitic.com/paper/8s9pjt3yhkbtt",
  "venue": "Molecular Therapy Oncology",
  "versions": []
}