vaccine therapy in treating lung cancer patients with cancer stem cells

Conditions: Neoplasms, Lung

Summary: most studies of cancer stem cells (csc) involve the inoculation of cells from human tumors into immunosuppressed mice, preventing an assessment on the immunologic interactions and effects of cscs. in this study, the investigators examined the vaccination effects produced by csc-enriched populations from histologically distinct murine tumors after their inoculation into different syngeneic immunocompetent hosts. enriched cscs were immunogenic and more effective as an antigen source than unselected tumor cells in inducing protective antitumor immunity.immune sera from csc-vaccinated hosts contained high levels of igg which bound to cscs, resulting in csc lysis in the presence of complement.ctls generated from peripheral blood mononuclear cells or splenocytes harvested from csc-vaccinated hosts were capable of killing cscs in vitro. mechanistic investigations established that csc-primed antibodies and t cells were capable of selective targeting cscs and conferring antitumor immunity.

to assess the feasibility of generating csc-loaded dc vaccines for clinical use, the investigators will harvest peripheral blood and tumor specimen from patients with lung cancer. the investigators will purify t, b cells and generate dcs from the pbmcs of the lung cancer patient.on the other hand, investigators will isolate aldhhigh and aldhlow tumor cells from the tumor specimen of the lung cancer patient using a similar protocol as investigators reported . aim 1: to demonstrate, in vitro, the relative cellular anti-lung cancer csc immunity induced by lung cancer csc-dc primed cytotoxic t cells. aim 2: to determine, in vitro, specific binding and lysis of lung cancer cscs by antibodies produced by purified b cells from pbmcs stimulated with lung cancer csc-dc.

Eligibility criteria:
inclusion criteria: 1. patients must have histologically or cytologically confirmed adenocarcinoma of the lung.the site of the primary lesion should be confirmed radiologically, or surgically to be in the lung. 2. patients must be deemed unresectable due to involvement of critical vasculature, adjacent organ invasion, presence of metastasis, or other medical condition making surgical resection unfavorable. 3. patients must have a primary or metastatic lesion measurable in at least one dimension by recist criteria within 4 weeks prior to entry of study . 4. more than 4 weeks must have elapsed from the time of major surgery or completion of the last dose of chemotherapy, radiation therapy, investigational therapy and patients must adequately recover from these effects. 5. life expectancy of \>3 months. 6. karnofsky performance status \>70%. 7. the patient shows normal organ function according to the following parameters(as measured within six weeks prior to treatment allocation): hemoglobin: within normal range according to institutional standards; absolute leukocyte count: within normal range according to institutional standards; absolute lymphocyte count: within normal range according to institutional standards; platelet count: within normal range according to institutional standards; alanine aminotransferase: ≤ 2.5 x upper limit of normal (uln); aspartate aminotransferase: ≤ 2.5 x uln; total bilirubin: ≤ 1.5 x uln. in the case of known gilbert's syndrome ≤ 2 x uln; serum creatinine: 1.5 x uln; calculated creatinine clearance: \> 50 ml/min . 8. age \>18 years. 9. no history of autoimmune diseases. 10. ability to understand the study protocol and a willingness to sign a written informed consent document. exclusion criteria: - 1. patients receiving anticoagulation therapy. 2. patients who have received prior gemcitabine or radiation therapy to the lung bed 3. patients receiving any other investigational agents. 4. patients with known brain metastases will be excluded because of their poor prognosis and because they often develop progressive neurological dysfunction that would confound the evaluation of neurological and other adverse effects. 5. uncontrolled concurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements. 6. patients who test positive for hepatitis b virus, hepatitis c virus or hiv. 7. level 3 hypertension; 8. severe coronary disease; 9. myelosuppression; 10. respiratory disease; 11. brain metastasis; 12. chronic infections