Abstract 956: HB-200: A novel viral vector vaccine platform that can improve immunotherapy treatment in HPV16+ HNSCC

Abstract Human papillomavirus-associated (HPV+) oropharyngeal squamous cell carcinoma (OSCC) is the most common head and neck cancer in the United States. While many HPV+ OSCC are curable using current standard treatment, the efficacy of these treatments diminishes when the cancers become metastatic. The viral associated malignancy provides unique opportunities for immunotherapy, however, immune checkpoint inhibitors only induce weak and unsustainable immunity against HPV+ cancer. Thus, there remains a need for new treatment modalities that improve outcomes while also reducing adverse effects. Previously, HB-200, a novel HPV-specific therapeutic vaccine containing two replicating live-attenuated vectors expressing the highly antigenic HPV16 E7E6 protein, has been shown to elicit a more robust anti-tumor immune response alongside chemotherapies compared to standard immunotherapies in clinical trial. However, the underlying mechanisms of why this vaccine can induce stronger immune response than immune checkpoint blockade remains unclear. Here, we utilize mouse models of HPV16 E6/E7+ OSCC to elucidate how HB-200 enhances anti-tumor immunity. To achieve this goal, we first established two complementary HPV16 E6/E7+ oral SCC tumor models: 1) grafting syngeneic MOC2 cells expressing the E6 and E7 oncoproteins of HPV16 on immune-competent C57BL/6 mice; 2) exposing the oral cavity of K14CreER; Rosa26-LSL-E6/E7 mice with 4-NQO to induce spontaneous oral SCCs. With these novel models, mice were then treated with either anti-PD-L1 or HB-200 plus chemotherapy to mimic clinical trials in humans. At 4 weeks post-tumor grafting, we profiled the immune landscape of these tumors by flow cytometry to quantify the frequency of specific CD8 T cell, CD4+ Tfh cell, and B cell populations which we hypothesized to be enriched following HB-200 treatment. This study addresses the central question of how viral immunotherapy can induce stronger immune responses than standard immune checkpoint immunotherapy and better enable T cells to achieve tumor control in HPV-associated cancer, providing an important mechanistic understanding of the HB-200 vaccine platform. Thus, findings from this study give critical insights for optimizing HPV-specific immunotherapy with the exciting potential to translate into novel clinical interventions for HPV+ OSCC patients. Citation Format: Sydney Fisher, Matthew Ji, Yuxuan Miao. HB-200: A novel viral vector vaccine platform that can improve immunotherapy treatment in HPV16+ HNSCC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 956.