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Dryad

Data from: Plant virus immunotherapy for HPV‐associated oropharyngeal squamous cell carcinoma

Affonso de Oliveira, Jessica Fernanda1; Opdensteinen, Patrick1; Simms, Andrea1; Jung, Seongwon1; Mognol, Giuliana P.2; Chen, Hui2; Varner, Judith A.2; Aagard, Marnie1; Steinmetz, Nicole F.1

Research facility: University of California San Diego
Published Aug 13, 2026 on Dryad. https://doi.org/10.5061/dryad.02v6wwqkc

Data files

Abstract

In high‐income countries, 60%–70% of oropharyngeal squamous cell carcinomas (OPSCCs) are attributable to human papillomavirus (HPV). Immunotherapy is the current second‐line treatment for advanced or metastatic cases of HPV + OPSCC; however, drug resistance, tumor heterogeneity, and adverse events limit efficacy and response. Here, we evaluated the drug candidate cowpea mosaic virus (CPMV) as an intratumoral (i.t.) immunotherapy in mouse E6/E7/hRas (mEER) models of HPV+ and HPV− OPSCC, focusing on efficacy and immune responses. These tumor models recapitulate key features of human disease, including oncogenes that drive tumor progression. Using a dose‐escalation strategy, CPMV achieved dose‐dependent control of HPV + tumors, with 50% tumor‐free survival by day 80. HPV − tumor growth was delayed but with minimal survival benefits. In a neoadjuvant setting (two 100 µg i.t. doses prior to tumor debulking), CPMV eradicated residual disease, with 75% of HPV + and 25% of HPV − mice remaining tumor-free. Early tumor profiling showed immune cell infiltration and remodeling of the HPV + tumor microenvironment (TME), including NK and myeloid cell recruitment and enrichment of CD4 + and CD8 + T cells within the TME. Multiplex cytokine analysis revealed ∼3‐fold increases in GM‐CSF, IL‐6, and MCP‐1 and ∼2‐fold increases in type I and II interferons, TNF‐α, and CCL3/MIP‐1α in HPV + tumors, consistent with innate activation and subsequent adaptive priming. Minor effects on the TME in the HPV − tumors suggest that tumor antigenicity may influence therapeutic outcomes. Overall, we demonstrated that CPMV i.t. immunotherapy elicits potent, durable antitumor immunity and TME remodeling in HPV + OPSCC, supporting further development as a neoadjuvant and local immunotherapy to address unmet clinical needs.