Active Immunization of Patients With Carcinoma of Oral Cavity or Oropharynx With Autologous Dendritic Cells Transfected With DNA From Autologous Tumor

This is an uncontrolled, non-randomized trial to evaluate safety, immunogenicity and
feasibility of a new vaccine, consisting of autologous monocyte-derived dendritic cells (DC)
transfected with autologous tumor-derived DNA. Briefly, the plan is to use a two-stage trial
design and to initially enroll 17 patients with primary advanced carcinoma of the oral
cavity or oropharynx over a period of 2 years. The patients will undergo surgery, and a
portion of the primary tumor specimen not necessary for the pathologic diagnosis will be
obtained to serve as a source of tumor DNA. Each DC-based vaccine will contain
DNA-transfected DC. It will be administered intranodally under ultrasound guidance. Only
those patients who have normal delayed type hypersensitivity (DTH) responses to recall
antigens will be eligible to receive the vaccine. Immunologic response to the vaccine will
be evaluated. If there is no evidence of toxicity, and >3 patients show immunologic
response, the second stage of the study will be opened for accrual of 22 patients. All
patients will be monitored by interferon- gamma (IFN-) secretion in enzyme-linked immunospot
(ELISPOT) assays prior to and after vaccination for the frequency of T-cells responsive to
autologous tumor and to the vaccine. The patients will also be evaluated before and after
vaccination for the capability of their T cells to respond to activating signals delivered
via the T cell receptor (TcR).

Primary Objective: To determine the safety and feasibility of immunization of patients with
carcinoma of the oral cavity or oropharynx with autologous monocyte-derived dendritic cells
(DC) transfected with DNA obtained from the patient's own cancer cells.

Secondary Objective: To evaluate the ability of the DNA-based DC vaccine to induce immune
responses to the vaccine as well as to autologous tumor.

Inclusion Criteria:

Written informed consent conforming to the institutional guidelines obtained from the
patient.

Documented evidence of oral carcinoma or carcinoma of the oropharynx. Patients will
undergo surgery, surgery and radiation or chemoradiation therapy, and will become eligible
for the first vaccine between 1and 4 months after termination of conventional therapy.

Adequate immune competence, as indicated by positive reaction to one or more of the DTH
skin tests.

Age 18 or above. Karnofsky performance status > 70% and life expectancy > eight months.

Adequate hematologic function:

Absolute neutrophil count > 1,000/mm3 Absolute lymphocyte count > 1,000/mm3 Hemoglobin > 9
g/dl Platelets > 100,000/mm3 h) Liver function tests: Bilirubin (total) < 1.7 mg/dl
Alkaline phosphatase < 78 u/L (2 x ULN) SGOT < 54 u/L (2 x ULN) Lactic dehydrogenase < 180
u/L (2 x ULN) i) Kidney profile: Serum electrolytes Sodium 135-145 mEq/L Potassium 3.5-5.0
mEq/L Bicarbonate 21-28 mEq/L Chloride 100-108 mmol/L 2) Serum creatinine <4.5 mg/dL (3 x
ULN) 3) BUN 8-25 mg/dL j) At least four weeks since any prior radiation therapy,
immunotherapy, or chemotherapy

Exclusion Criteria:

- One or more of the Inclusion Criteria are not met. A significant history or current
evidence of cardiac disease including, but not limited to, congestive heart failure,
coronary artery disease, angina pectoris, uncontrolled hypertension, serious arrhythmias;
or myocardial infarction within the previous six months.

Evidence of active infection requiring antibiotic therapy. Positive HIV or Hepatitis B or
C screen tests Active intracranial metastases. Previously resected intracranial disease
and or previously irradiated intracranial metastases which have been stable for four weeks
are eligible.

History of other concurrent malignancies except basal cell carcinoma, squamous cell
carcinoma of the skin, or carcinoma in situ of the cervix.

Pregnant or lactating women. Patients requiring systemic corticosteroids (unless patient
has had NO STEROIDS IN THE PAST 4 WEEKS).

Autoimmune disease including, but not limited to, rheumatoid arthritis, systemic lupus
erythematous, multiple sclerosis, or ankylosing spondylitis