BACKGROUND: One of the important mechanisms responsible for a tumor escaping the immune response is an absence of the tumor associated antigen (TAA) on the cancer cell surface. To overcome this, combination gene therapy using a herpes simplex thymidine kinase (HSTK) gene, prototype of drug sensitizing gene, was conducted to enhance TAA release by cell destruction, as well as the cytokine genes for immune cell attraction. METHODS: We investigated whether or not transduction with the adenovirus-HSTK (Ad-HSTK) enhanced the sensitivity of Lewis lung carcinoma (LLC) to ganciclovir (GCV) and induced a bystander effect. A Tumor vaccine trial was performed using LLC with ad-HSTK ±ad-GM-CSF±ad-IL-2 to determine if they exhibit some antitumor effect on established lung cancer xenografts. RESULTS: LLC with ad-HSTK revealed a much higher sensitivity to ganciclovir (GCV). LLC transduced with ad-HSTK and/or ad-IL-2, ad-GM-CSF showed a lower in vivo tumorigenicity. In the treatment experiment, vaccination with LLC transduced with ad-HSTK, ad-IL-2, or ad-GM-CSF alone modestly suppressed the growth of an established tumor. Combined transduction with HSTK and GM-CSF induced stronger growth suppression of a established lung cancer, while HSTK and IL-2 combination transduction did not have any antitumor effect on individual transduction. Vaccination with LLC-HSTK-GM-CSF increased the infiltration of dendritic cells in the spleen. CONCLUSION: It was concluded that a tumor vaccine transduced with HSTK and GM-CSF induces strong antitumor immunity by activating the dendritic cells.
Adenoviridae ; Animals ; Bystander Effect ; Carcinoma, Lewis Lung ; Cytokines* ; Dendritic Cells ; Ganciclovir ; Genetic Therapy* ; Granulocyte-Macrophage Colony-Stimulating Factor ; Herpes Simplex* ; Heterografts ; Interleukin-2 ; Lung Neoplasms* ; Lung* ; Phosphotransferases* ; Simplexvirus* ; Spleen ; Thymidine Kinase ; United Nations ; Vaccination

Pulmonary alveolar proteinosis is such an extremely rare disease in Korea, that only a few cases have been reported. Meanwhile five cases were experienced at Seoul National University Hospital over ten years since 1987. We summarized the clinical characteristics and courses of them. Seven cases reported in the literature were included to add data about clinical characteristics and courses although only a few case reports mentioned patient's course. Middle aged male patients were mainly affected. No association with particular environmental or occupational exposure was identified. Dyspnea on exertion was the main symptom. Bilateral crackles were consistent, and bilateral parahilar hazy infiltrations on plain chest radiograph and ground glass opacity on high-resolution CT were characteristic. Superimposed infection was not identified in any patient at the time of diagnosis. Decreased diffusing capacity and hypoxia were present in almost every case. Whole lung lavage proved to be an effective therapeutic measure. The response to treatment was good. Long-term course of the disease, e.g. recurrence rate, is not yet known.
Adult ; Age Distribution ; Aged ; Female ; Hospitals, Public* ; Hospitals, University* ; Human ; Korea ; Male ; Middle Age ; Pulmonary Alveolar Proteinosis/therapy ; Pulmonary Alveolar Proteinosis/radiography ; Pulmonary Alveolar Proteinosis/physiopathology* ; Pulmonary Alveolar Proteinosis/diagnosis ; Sex Distribution ; Smoking/adverse effects