Oral squamous cell cancer (OSCC) is the sixth most common cancer worldwide and accounts for 2% of all malignancies in the USA. In this year alone, 40,000 men and women will develop OSCC, and unfortunately, only two-thirds of these OSCC patients will survive more than five years. While the past decades have seen advances in ablative/reconstructive surgery, radiation therapy, and chemotherapy, the overall survival rate of OSCC patients has not improved significantly, and there are multiple co-morbidities which arise from treatment which may negatively affect quality of life. Thus, there is a real need for innovative new approaches to treating oral squamous cell cancer. Cancer immunotherapy has arisen as a novel treatment modality for several cancers, and an implantable, polymeric cancer vaccine has been developed by the Mooney laboratory which shows impressive tumor killing in both melanoma and glioma preclinical models. Our goal is to evaluate this promising cancer vaccine technology for use in oral squamous cell carcinoma. Our overall hypothesis is that an in situ cancer vaccine construct able to provide appropriate spatiotemporal presentation of bioactive factors to host dendritic cells can induce anti-tumor immunity. The studies outlined in this proposal seek to determine the effectiveness of the implantable cancer vaccine for treating OSCC, to optimize the various components of the cancer vaccine for maximum potency, and to explore any synergistic effects which arise by combining this vaccine with other immunotherapeutic tools such as tumor-specific monoclonal antibodies. Overall, these studies are anticipated to enhance our understanding of the role dendritic cells and tumor-specific cytotoxic T cells play in the treatment of OSCC, and may also contribute to the development of novel immunotherapies for OSCC.

Public Health Relevance

Despite advances in surgical techniques, methods of radiation therapy, and chemotherapeutic strategies, the overall 5-year survival rate for oral squamous cell cancer has not improved much over the last few decades. In addition, the potential morbidities associated with conventional multimodal treatment can have an adverse impact on quality of life. The goal of this proposal is to investigate the effectiveness of an implantable cancer vaccine that is designed to generate a potent anti-tumor immune response as a novel treatment for oral squamous cell cancer.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Career Transition Award (K99)
Project #
5K99DE023577-02
Application #
8701276
Study Section
NIDR Special Grants Review Committee (DSR)
Program Officer
Frieden, Leslie A
Project Start
2013-08-26
Project End
2015-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Harvard Medical School
Department
Dentistry
Type
Schools of Dentistry/Oral Hygn
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02115
Leach, David G; Dharmaraj, Neeraja; Piotrowski, Stacey L et al. (2018) STINGel: Controlled release of a cyclic dinucleotide for enhanced cancer immunotherapy. Biomaterials 163:67-75