Methods Patient Characteristics Patients who met the following eligibility criteria were included: histopathologically confirmed diagnosis of advanced NSCLC (stage IIIB-IV)[6]; aged ≤70 years; performance status ≤2[7]; no prior chemotherapy, surgery, or radiotherapy; no central nervous
system metastases and at least one measurable lesion according to the RECIST’s criteria[8]; no associated acute disease; HLA-A2 OSI-027 molecular weight phenotype and expression of WT1 (Wilms Tumor Protein), HER-2 (Human Epidermal Growth Factor Receptor 2), CEA (Carcinoembryonic Antigen) or MAGE1 (Melanoma Antigen 1) proteins at the tumor site (tissue). The phenotype HLA-A2 was chosen due the methodology adopted for the incorporation of the antigen to the dendritic cell. The maintenance of organic functions was confirmed by: white blood cells (WBC) ≥3000/mm3, neutrophil cells ≥1500/mm3, hemoglobin (Hgb) ≥9.0 g/dL, and Torin 2 solubility dmso platelets ≥100,000/mm3; bilirubin ≤1.5 mg/dL, aspartate aminotransferase ≤40 IU/L; creatinine clearance >55 mL/minute. The written informed consent was obtained from all patients enrolled in the study. The study was conducted in accordance with the International Conference on Harmonization
(ICH) guidelines, applicable regulations and the guidelines governing the clinical study conduct and the Pifithrin-�� chemical structure ethical principles of the Declaration of Helsinki. Trial Design The trial was nonrandomized. All selected patients received conventional treatment (chemotherapy with or without radiotherapy). Briefly, the chemotherapy protocols included paclitaxel 175 mg/m2 and cisplatinum 70 mg/m2 on day 1. These cycles were then repeated four times every 21 days. After the forth chemotherapeutical 3-mercaptopyruvate sulfurtransferase cycle, the patients were submitted to computed tomography (CT) scan of thorax, abdomen and brain to evaluate the tumor response. The progressive disease was an exclusion criterion. Patients who met all criteria for inclusion were eligible to the dendritic cells vaccine as an adjuvant therapy, which was administered after hematological
recovery (platelets ≥70,000/mm3). The measurable immunologic response and safety to the vaccine were the primary and secondary endpoints. The small sample size could preclude meaningful assessment of therapeutic effects. The clinical tolerability was determined by routine safety laboratories and the clinical events described by the Cancer Therapy Evaluation Program (CTEP), and Common Terminology Criteria for Adverse Events (CTCAEv3)[9]. The steps of the study are showed in figure 1. Figure 1 The steps of the study. Leukapheresis’ day is marked with “”L”" (D-7 and D7). Immunizations’ day is marked with “”V”" (D0 and D14). Blue triangle – Evaluation step: “”Dx+S1″” = Diagnosis and 1st Radiologic Staging; “”S2″” = 2nd Radiologic Staging (1 month after conventional treatment); “”S3″” = 3rd Radiologic Staging (1 month after vaccine); “”S4…