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Characterization of recombinant gorilla adenovirus HPV therapeutic vaccine PRGN-2009
Samuel T Pellom1, Claire Smalley Rumfield1, Y Maurice Morillon1
1Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute (NCI), NIH, Bethesda, Maryland, USA.
Abstract:
There are approximately 44,000 cases of human papillomavirus-associated (HPV-associated) cancer each year in the United States, most commonly caused by HPV types 16 and 18. Prophylactic vaccines successfully prevent healthy people from acquiring HPV infections via HPV-specific antibodies. In order to treat established HPV-associated malignancies, however, new therapies are necessary. Multiple recombinant gorilla adenovirus HPV vaccine constructs were evaluated in NSG-β2m-/- peripheral blood mononuclear cell-humanized mice bearing SiHa, a human HPV16+ cervical tumor, and/or in the syngeneic HPV16+ TC-1 model. PRGN-2009 is a therapeutic gorilla adenovirus HPV vaccine containing multiple cytotoxic T cell epitopes of the viral oncoproteins HPV 16/18 E6 and E7, including T cell enhancer agonist epitopes. PRGN-2009 treatment reduced tumor volume and increased CD8+ and CD4+ T cells in the tumor microenvironment of humanized mice bearing the human cervical tumor SiHa. PRGN-2009 monotherapy in the syngeneic TC-1 model also reduced tumor volumes and weights, generated high levels of HPV16 E6-specific T cells, and increased multifunctional CD8+ and CD4+ T cells in the tumor microenvironment. These studies provide the first evaluation to our knowledge of a therapeutic gorilla adenovirus HPV vaccine, PRGN-2009, showing promising preclinical antitumor efficacy and induction of HPV-specific T cells, along with the rationale for its evaluation in clinical trials.
Insights
A novel therapeutic vaccine, PRGN-2009, shows promise in treating human papillomavirus (HPV)-associated cancers. This gorilla adenovirus vaccine effectively reduced tumor size and boosted anti-cancer T cells in preclinical models.
Area of Science:
- Oncology
- Immunology
- Vaccinology
Background:
- Human papillomavirus (HPV)-associated cancers represent a significant public health burden, with approximately 44,000 cases annually in the U.S.
- Current prophylactic HPV vaccines are effective at preventing infection but not for treating established HPV-associated malignancies.
- Novel therapeutic strategies are crucial for addressing existing HPV-driven tumors.
Purpose of the Study:
- To evaluate the preclinical efficacy of PRGN-2009, a novel recombinant gorilla adenovirus-based therapeutic HPV vaccine.
- To assess the vaccine's ability to induce HPV-specific T cell responses and reduce tumor burden in relevant animal models.
Main Methods:
- PRGN-2009 was tested in two models: humanized mice bearing SiHa (HPV16+ cervical tumor) and a syngeneic HPV16+ TC-1 mouse model.
- Tumor volume, weight, and immune cell infiltration (CD8+ and CD4+ T cells) within the tumor microenvironment were analyzed post-treatment.
Main Results:
- PRGN-2009 treatment significantly reduced tumor volume in humanized mice and decreased tumor volumes and weights in the TC-1 model.
- The vaccine increased the presence of CD8+ and CD4+ T cells within the tumor microenvironment in both models.
- High levels of HPV16 E6-specific T cells and multifunctional CD8+ and CD4+ T cells were observed.
Conclusions:
- PRGN-2009 demonstrates promising preclinical antitumor efficacy against HPV-associated cancers.
- The vaccine effectively induces HPV-specific T cell responses, supporting its potential as a therapeutic agent.
- These findings provide a strong rationale for the clinical evaluation of PRGN-2009 in patients with HPV-associated malignancies.
