Biological Vaccine: Semi-allogeneic Human Fibroblasts (MRC-5) Transfected With DNA

This is a single institution open-label phase Ib clinical trial designed to determine the
safety of immunization of patients with resected Head and Neck Squamous Cell Carcinoma
(HNSCC) with lethally irradiated semi-allogeneic human fibroblasts (MRC-5) transfected with
DNA derived from the subject's own tumor and to measure the immune response to the
autologous tumor vaccine.

Briefly, the plan is to use a two-stage trial design and to initially enroll 15 patients
with Head and Neck Squamous Cell Carcinoma (HNSCC). The patients will undergo surgical
resection to provide complete removal of the primary lesion with negative gross and
microscopic margins. A portion of the primary tumor specimen not necessary for the
pathologic diagnosis will be obtained to serve as a source of DNA for preparing the vaccine.
Each DNA-based vaccine will contain 1 x 10e7 DNA-transfected human allogeneic fibroblasts.
The vaccine will be lethally irradiated before it is used for immunization. It will be
administered intradermally in the Outpatient Clinic for a total of four vaccinations
delivered at weekly intervals.

Patients delayed-type hypersensitivity (DTH) responses will be tested but will not be an
eligibility criterion. Immunologic response to the vaccine will be evaluated. If there is no
evidence of toxicity, and >3 of the 15 initial patients show immunologic response, the
second stage of the study will be opened for accrual of 22 patients.

To determine patient's response to the DNA-based vaccines, the frequency of T cells reactive
with recipient cells transfected with the autologous tumor DNA will be measured by ELISPOT
for IFN-y and compared with the response to non-transfected fibroblasts prior to and after
vaccination. All patients will be monitored for Immunologic response by assays include
ELISPOT, flow cytometry for lymphocyte markers, Annexin V binding, TcR expression, caspase3
activity and serum antibodies.

Inclusion Criteria:

- Pathological stage I-IVa HNSCC

- The subject must have a complete removal of the primary HNSCC lesion with negative
gross and microscopic margins. Documentation of margins by frozen sections at surgery
is recommended. Patients who have already had surgery and have available banked tumor
samples can be enrolled AFTER surgery.

- At least 18 years of age.

- Karnofsky performance status >/= 70

- Adequate hematologic function:

- Absolute neutrophil count > 1,000/mm3

- Absolute lymphocyte count > 1,000/mm3

- Hemoglobin > 9 g/dL

- Platelets > 100,000/mm3

- Liver function tests:

- Bilirubin (total) < /=1.7 mg/dL

- Alkaline phosphatase < 252 u/L

- SGOT < 108 u/L

- Kidney profile:

- Serum electrolytes

- Sodium 136-146 mEq/L

- Potassium 3.5-5.0 mEq/L

- Bicarbonate 21-31 mEq/L

- Chloride 98-107 mmol/L

- Serum creatinine < 3 x ULN

- BUN 8-26 mg/dL

- At least a 12 week interval should have elapsed between prior surgery, radiation
therapy, chemotherapy or any other treatment and the first vaccination. Patients
should have recovered from surgery and adjuvant treatment.

- The effects of the tumor DNA-transfected fibroblast vaccine on the developing human
fetus are unknown. For this reason women of child-bearing potential must agree to use
adequate contraception (hormonal or barrier method of birth control; abstinence)
prior to study entry, for the duration of study participation and for 4 months after
the last dose of the study vaccine, even if oral contraceptives are used. Should a
woman become pregnant or suspect she is pregnant while she or her partner is
participating in this study, she should inform her treating physician immediately.
Men treated or enrolled on this protocol must also agree to use adequate
contraception prior to the study, for the duration of study participation, and 4
months after completion of the tumor DNA-transfected fibroblast vaccine
administration.

Exclusion Criteria:

Patients will be EXCLUDED from participation in the study if any of the following apply:

- 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 ongoing or active infection requiring antibiotic therapy.

- Active intracranial metastases. Patients with previously resected intracranial
disease and/or previously irradiated intracranial metastases that have been
clinically stable for four weeks are eligible.

- Pregnant or lactating women. Pregnant women are excluded from this study. Women of
childbearing potential must have a negative pregnancy test per standard of care prior
to the surgery for tumor removal. A second pregnancy test must be performed 7 days
prior to the first vaccination and must be negative. Because there is an unknown but
potential risk for adverse events in nursing infants secondary to treatment of the
mother, breastfeeding should be discontinued if the mother is treated on study.

- Patients requiring systemic corticosteroids (unless patients have had no
corticosteroids within 4 weeks prior to start of study).

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

- Patients who have post-obstructive pneumonia or other serious infection at the time
of registration or other serious underlying medical condition that would impair the
ability of the patient to receive protocol treatment.

- No prior malignancy is allowed except for adequately treated basal cell or squamous
cell skin cancer, in situ cervical cancer, or other cancer from which the patient has
been disease-free for at least 5 years prior to registration.

- Uncontrolled intercurrent illness including, but not limited to psychiatric
illness/social situations that would limit compliance with study requirements.

- HIV-positive patients receiving combination anti-retroviral therapy are excluded from
the study. HIV testing will be performed in patients receiving combination
anti-retroviral therapy when indicated per medical records review.

- Patients with clinical symptoms of Hepatitis B and/or Hepatitis C will be tested, if
clinically indicated per medical records review. Positive results will be an
exclusion criteria