CD4+ T cells are required for tumor antigen-expressing oHSV glioma therapeutic effect and antigen-specific antibody production
7 affiliations
- 1Center for Childhood Cancer Research, Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH 43215, USA
- 2Medical Scientist Training Program, The Ohio State University College of Medicine, Columbus, OH 43210, USA
- 3Biomedical Sciences Graduate Program, The Ohio State University College of Medicine, Columbus, OH 43210, USA
- 4Division of Hematology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA
- 5Department of Microbial Infection and Immunity, The Ohio State University College of Medicine, Columbus, OH 43210, USA
- 6Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43210, USA
- 7Department of Pediatrics, Division of Pediatric Infectious Diseases, Nationwide Children’s Hospital, Columbus, OH 43205, USA
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.
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BibTeX
@article{hernandezaguirre2026cells,
title = {{CD4+ T cells are required for tumor antigen-expressing oHSV glioma therapeutic effect and antigen-specific antibody production}},
author = {Ilse Hernandez-Aguirre and Doyeon Kim and Jack Hedberg and Alexia K. Martin and Yeaseul Kim and Phillip Perez and Gregory Behbehani and Gang Xin and Kevin A. Cassady and Ravi Dhital},
journal = {Molecular Therapy Oncology},
year = {2026},
month = sep,
doi = {10.1016/j.omton.2026.201353},
url = {https://doi.org/10.1016/j.omton.2026.201353},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - CD4+ T cells are required for tumor antigen-expressing oHSV glioma therapeutic effect and antigen-specific antibody production
AU - Ilse Hernandez-Aguirre
AU - Doyeon Kim
AU - Jack Hedberg
AU - Alexia K. Martin
AU - Yeaseul Kim
AU - Phillip Perez
AU - Gregory Behbehani
AU - Gang Xin
AU - Kevin A. Cassady
AU - Ravi Dhital
PY - 2026
DA - 2026/09/29
JO - Molecular Therapy Oncology
DO - 10.1016/j.omton.2026.201353
UR - https://doi.org/10.1016/j.omton.2026.201353
AB - 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.
SN - 2950-3299
ER -