Career Development Program
Project Three: Dendritic Cell Vaccines for the Treatment of Head and Neck Squamous Cell Carcinoma
Jeffrey Moyer, M.D.
Our laboratory investigations have centered on the anti-tumor effects of dendritic cell vaccines. Recently, we performed experiments examining the role of dendritic cell vaccines in the setting of immune suppression induced by total body irradiation. These studies documented the ability to prime an effective, tumor-specific immune response during significant T cell depletion. Additional experiments performed in the laboratory of Dr. Alfred Chang have demonstrated that radiation causing transient lymphodepletion can potentiate the antitumor effects of dendritic cell vaccines. Based on the findings in our laboratory as well as data from other preclinical and clinical studies, we believe that the lymphocyte-depleted state generated by therapeutic chemotherapy and radiation offers a unique opportunity to use adjuvant dendritic cell immunotherapy. We propose a series of experiments that will assess the utility of this treatment approach in a preclinical model of head and neck squamous cell carcinoma.
Specific Aims are:
- Determine the appropriate dosing regimens to cause lympho[penia using concurrent chemotherapy and radiation in a mouse model of head and neck cancer.
- Determine the antitumor efficacy of intratumoral dendritic cell vaccines in the setting of concurrent chemotherapy and radiation in the lymphopenic host.
- Investigate the impact of concurrent chemoradiation and intratumor dendritic cell vaccines on systemic antitumor immunity in the lymphopenic host.