Immunization of Patients With Non Small Cell Lung Cancer (NSCLC)

This is an uncontrolled, non-randomized trial to evaluate safety, immunogenicity and
feasibility of a new vaccine, consisting of semi-allogeneic fibroblasts transfected with
autologous tumor-derived DNA. Briefly, the plan is to use a two-stage trial design and to
initially enroll 15 patients with non small cell lung cancer (NSCLC) 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 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. 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. All patients will be monitored by IFN-g secretion in
ELISPOT assays prior to and after vaccination for the frequency of T-cells responsive to
autologous tumor (if available) and/or 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).

Inclusion Criteria:

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

- A diagnosis of non-small cell lung cancer (NSCLC), subjects will undergo or have had
surgical resection.

- Age 18 or above.

- 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 vaccination and any prior
radiation therapy, chemotherapy or any other treatment. Patients should have
recovered from surgery and adjuvant treatment.

Exclusion Criteria:

Subjects 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 arrythmias or myocardial infarction within the
previous six months.

- Evidence of active infection requiring antibiotic therapy.

- Active intracranial metastases. Patients with previously resected intracranial
disease and/or previously irradiated intracranial metastases that have been 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. 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 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

- Patient must not 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.

- Subject is not a candidate for complete resection of the carcinoma via pneumonectomy,
lobectomy, bilobectomy, extended wedge resection or anatomic segmentectomy with or
without sleeve resection as noted in the surgical plan..

- Prior resection of lung cancer is allowed, if at least five years have elapsed
between previous resection and registration.

- 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, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.