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Allogeneic gene-modified tumor cells (RCC-26/IL-7/CD80) as a vaccine in patients with metastatic renal cell cancer: a clinical phase-I study.
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|Title: ||Allogeneic gene-modified tumor cells (RCC-26/IL-7/CD80) as a vaccine in patients with metastatic renal cell cancer: a clinical phase-I study.|
|Affiliation: ||Department of Hematology, Oncology and Tumor Immunology, Charité-University Medicine Berlin, Campus Virchow-Klinikum and Campus Berlin-Buch, Berlin, Germany. firstname.lastname@example.org|
|Citation: ||Allogeneic gene-modified tumor cells (RCC-26/IL-7/CD80) as a vaccine in patients with metastatic renal cell cancer: a clinical phase-I study. 2011, 18 (4):354-63 Gene Ther.|
|Journal: ||Gene therapy|
|Issue Date: ||Apr-2011 |
|PubMed ID: ||21068778|
|Abstract: ||Despite novel targeted agents, prognosis of metastatic renal cell cancer (RCC) remains poor, and experimental therapeutic strategies are warranted. Transfection of tumor cells with co-stimulatory molecules and/or cytokines is able to increase immunogenicity. Therefore, in our clinical study, 10 human leukocyte antigen (HLA)-A(*)0201(+) patients with histologically-confirmed progressive metastatic clear cell RCC were immunized repetitively over 22 weeks with 2.5-40 × 10(6) interleukin (IL)-7/CD80 cotransfected allogeneic HLA-A(*)0201(+) tumor cells (RCC26/IL-7/CD80). Endpoints of the study were feasibility, safety, immunological and clinical responses. Vaccination was feasible and safe. In all, 50% of the patients showed stable disease throughout the study; the median time to progression was 18 weeks. However, vaccination with allogeneic RCC26/IL-7/CD80 tumor cells was not able to induce TH1-polarized immune responses. A TH2 cytokine profile with increasing amounts of antigen-specific IL-10 secretion was observed in most of the responding patients. Interferon-γ secretion by patient lymphocytes upon antigen-specific and non-specific stimulation was substantially impaired, both before and during vaccination, as compared with healthy controls. This is possibly due to profound tumor-induced immunosuppression, which may prevent induction of antitumor immune responses by the gene-modified vaccine. Vaccination in minimal residual disease with concurrent depletion of regulatory cells might be one strategy to overcome this limitation.|
Carcinoma, Renal Cell
Cell Line, Tumor
|Appears in Collections: ||Publications of Dept. Chemical Biology (CBIO)|
|Files in This Item:|
|Westermann et al_final.pdf||original manuscript||376Kb||Adobe PDF|
|Figure 1 A+B.pdf||figure 1||66Kb||Adobe PDF|
|Figure 2.pdf||figure 2||2968Kb||Adobe PDF|
|Figure 3.pdf||figure 3||95Kb||Adobe PDF|
|Figure 4.pdf||figure 4||51Kb||Adobe PDF|
|Figure 5.pdf||figure 5||131Kb||Adobe PDF|
|Figure 6 A+B.pdf||figure 6||43Kb||Adobe PDF|
|Table 1.pdf||table 1||42Kb||Adobe PDF|
|Table 2.pdf||table 2||55Kb||Adobe PDF|
|Table 3.pdf||table 3||40Kb||Adobe PDF|
|Table 4.pdf||table 4||59Kb||Adobe PDF|
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