As is the case with other solid tumors, lung cancer by themselves may be poorly immunogenic, but can become potent vaccines if modified to increase their immunoge-nicity. For example, modification of lung cancers with the the costimulatory molecule CD80 results in a greater ability to active CTL in vitro (53). In a phase I/II trial for patients with stage IV or relapsed NSCLC, an allogeneic, irradiated lung adenocarcinoma cell line transfected with CD80 and human leukocyte antigen (HLA)-A1 or -A2 was administered subcutaneously to 12 patients (54). There was one partial response and three with stable disease lasting 7-12+ mo. Three of these patients also showed significant increases (44-to 267-fold) in tumor-specific CD8 CTLs, measured by interferon (IFN)-gamma ELISPOT assay. Nemunaitis and colleagues (55) performed a phase I/II study of autologous lung cancers modified with an adenoviral vector encoding granulocyte-macrophage colony-stimulating factor (GM-CSF) (GVAX). A challenge for these studies is obtaining an adequate number of cells and successfully modifying a majority of the tumor cells. In this study, 78% of the tumors were successfully modified and a median dose of 1.3 x 107 cells were produced. At the time of the report, 12 patients had been treated and 6 completed the immunizations. Of three patients with advanced measurable disease who completed the therapy, there was one complete response, one minor response, and one stable disease. A possible solution to the complexities of reliably modifying autologous tumor is to mix autologous tumor cells with bystander cells (K562) that are gene modified to secrete GM-CSF (56). The bystander cells produce much higher amounts of GM-CSF with less lot-to-lot variability. A solution to the difficulty in obtaining adequate numbers of autologous tumor is to use allogeneic cell lines transfected with immunostimulatory genes.
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