Active Immunization of Patients With Carcinoma of Oral Cavity or Oropharynx With Autologous Dendritic Cells Transfected With DNA From Autologous Tumor
Active Immunization of Patients With Carcinoma of Oral Cavity or Oropharynx With Autologous Dendritic Cells Transfected With DNA From Autologous Tumor
The primary goal of this study is to determine if the vaccine can be safely given to
 subjects, and to see what side effects occur (both good and bad) when they are given this
 experimental tumor vaccine. During this study, investigators intend to watch for tumor
 response while examining the effects of this vaccine on the body's immune system after it is
 given.
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