A growing subset of head and neck cancers are caused by infection with the human papillomavirus (HPV) type-16. There is a strong need to develop novel treatment strategies which take advantage of the unique tumor biology of this patient cohort. HPV-specific vaccines represent such a promising, targeted adjuvant treatment option. We plan to evaluate a DNA vaccine, pNGVL4a-CRT/E7(detox) DNA, in combination with various strategies that can further enhance its potency. In addition to evaluating the safety of the novel DNA vaccine, we plan to measure immunologic responses and characterize tumor infiltrating immune cells within pathologic specimens which will be obtained before and after DNA vaccination as part of routine standard of care. This will give us an opportunity to better understand how this environment may change after vaccination, which will be critical to successful immunotherapy translation. The results of this phase I clinical trial will facilitate a subsequent phase II clinical trial which will evaluate the efficacy of the vaccine in generating HPV-specific CD8+ T cell immune responses which can potentially impact the survival in this patient population by providing long-term immune protection against the development of locoregional recurrence and/or micrometastatic disease. The strengths of our application include the availability of GMP grade reagents developed by the research team and NCI RAID, and previous experience in DNA vaccine clinical trial design and execution with an infrastructure in place at our institution which facilitates further investigation into this area. In addition, we have support from the institution to conduct this clinical trial and access to supportive collaborators who are also evaluating human immune responses elicited after vaccination. The project challenges existing paradigms by coupling chemoradiation treatment with immunotherapy in order to achieve a more potent immunologic response. The results gained from this study will advance the field of immunotherapy by providing information which will allow us to re-evaluate our current strategies to enhance vaccine potency.

Public Health Relevance

Human papillomavirus associated head and neck cancer represents a growing patient population. The biology of these tumors provides a unique opportunity to develop novel targeted treatments. We propose to evaluate a therapeutic HPV vaccine in combination with chemoradiation therapy and other various strategies that may enhance the efficacy of the vaccine in this patient cohort..

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Specialized Center (P50)
Project #
5P50DE019032-12
Application #
8529491
Study Section
Special Emphasis Panel (ZCA1-RPRB-7)
Project Start
Project End
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
12
Fiscal Year
2013
Total Cost
$344,687
Indirect Cost
$117,416
Name
Johns Hopkins University
Department
Type
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Kelley, Dylan Z; Flam, Emily L; Guo, Theresa et al. (2018) Functional characterization of alternatively spliced GSN in head and neck squamous cell carcinoma. Transl Res 202:109-119
Ghantous, Yasmine; Schussel, Juliana L; Brait, Mariana (2018) Tobacco and alcohol-induced epigenetic changes in oral carcinoma. Curr Opin Oncol 30:152-158
Gleber-Netto, Frederico O; Zhao, Mei; Trivedi, Sanchit et al. (2018) Distinct pattern of TP53 mutations in human immunodeficiency virus-related head and neck squamous cell carcinoma. Cancer 124:84-94
Kagohara, Luciane T; Stein-O'Brien, Genevieve L; Kelley, Dylan et al. (2018) Epigenetic regulation of gene expression in cancer: techniques, resources and analysis. Brief Funct Genomics 17:49-63
Windon, Melina J; D'Souza, Gypsyamber; Rettig, Eleni M et al. (2018) Increasing prevalence of human papillomavirus-positive oropharyngeal cancers among older adults. Cancer 124:2993-2999
Ravi, Rajani; Noonan, Kimberly A; Pham, Vui et al. (2018) Bifunctional immune checkpoint-targeted antibody-ligand traps that simultaneously disable TGF? enhance the efficacy of cancer immunotherapy. Nat Commun 9:741
Bishop, Justin A; Westra, William H (2018) MYB Translocation Status in Salivary Gland Epithelial-Myoepithelial Carcinoma: Evaluation of Classic, Variant, and Hybrid Forms. Am J Surg Pathol 42:319-325
Pai, Sara I; Jack Lee, J; Carey, Thomas E et al. (2018) HLA class I antigen processing machinery (APM) component expression and PD-1:PD-L1 pathway activation in HIV-infected head and neck cancers. Oral Oncol 77:92-97
Bishop, Justin A; Rooper, Lisa M; Chiosea, Simion I et al. (2018) Clear Cell Carcinoma of Salivary Glands Is Frequently p16 Positive: A Pitfall in the Interpretation of Oropharyngeal Biopsies. Am J Surg Pathol 42:367-371
Afsari, Bahman; Guo, Theresa; Considine, Michael et al. (2018) Splice Expression Variation Analysis (SEVA) for inter-tumor heterogeneity of gene isoform usage in cancer. Bioinformatics 34:1859-1867

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