This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a single-center, open-label, uncontrolled, out patient, ascending dose, parallel group study in male and female patients aged 18 or older with MAGE-A3- and/or HPV 16-positive SCC of the head and neck. Subjects who meet the inclusion and exclusion criteria will be assigned to Cohort 1 if they are HPV 16 positive and to Cohort 2 if they are MAGE-A3 positive and will be treated with HPV 16 Trojan peptide vaccine (Cohort 1) or MAGE-A3 Trojan peptide vaccine (Cohort 2). If patients are positve for both MAGE-A3 and HPV 16 antigens they will be assigned to the group with the fewest number of participants. Cohorts 1 and 2 will run independently of each other. Three dose levels of HPV 16 Trojan peptide vaccine or MAGE-A3 Trojan peptide vaccine (500 micrograms, 1000 micrograms, 1500 micrograms) will be tested in sequential groups of subjects (3 per dose level) within each cohort. Each subject will receive subcutaneous injections of their allocated dose level of HPV 16 or MAGE A3 Trojan peptide vaccine, which will be injected with fixed doses of the adjuvants Montanide (1.2 mL) and GM-CSF (100 micrograms/m2). A total of four vaccinations will be administered at 2-week intervals. PRIMARY OBJECTIVES 1. Determine the Adequate Biologic Dose The primary objective of this study is to establish the adequate biologic dose for this vaccine. The adequate biologic dose is defined as the dose at which the majority of patients expresses at least a 5 fold increase in response to Trojan peptides 0001 and 0002 after the first vaccination as measured by IFN-? and ELISPOT analysis. 2. Confirm Safety This study will to confirm the safety of the dosages and schedules as described in protocol section 5.2 and 6.2. Based upon prior trials, we do not anticipate that these vaccines will result in serious toxicity. SECONDARY OBJECTIVES 1. Tumor Response Tumor response, as assessed by RECIST. 2. Tumor Infiltrating Lymphocytes Immunohistochemical analysis will be performed to assess the degree of tumor infiltration by lymphocytes pre- and post-treatment, if possible. 3. Overall Survival Progression free and overall survival will be determined. 4. We will correlate immunologic and clinical response with HLA-A2. Given the small numbers, this will be exploratory as we will lack statistical power to make definitive conclusions.
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