Medizinische Universität Graz - Research portal
Selected Publication:
Schoell, WM; Mirhashemi, R; Liu, B; Janicek, MF; Podack, ER; Penalver, MA; Averette, HE.
Generation of tumor-specific cytotoxic T lymphocytes by stimulation with HPV type 16 E7 peptide-pulsed dendritic cells: an approach to immunotherapy of cervical cancer.
Gynecol Oncol. 1999; 74(3):448-455
Doi: 10.1006/gyno.1999.5504
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- Leading authors Med Uni Graz
- Schöll Wolfgang
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- Abstract:
- OBJECTIVE: The aim of this study was to generate HPV-16 E7 peptide-specific cytotoxic T lymphocytes (CTLs) in vitro for future adoptive immunotherapy of cervical cancer. METHODS: Peripheral blood mononuclear cells (PBMC) were isolated from HLA-A2+ healthy donors. The PBMCs were incubated with HPV-16 E7(11-20) peptide and varying cytokines in the primary culture. Restimulation was performed weekly with peptide-pulsed, irradiated autologous PBMCs. Alternatively, the PBMCs were depleted of abundant CD4+ cells and stimulated with HPV-16 E7(11-20) peptide-pulsed dendritic cells. Cytolytic activity was determined by a standard 4-h (51)Cr-release assay. RESULTS: After 6 weeks in culture, we were able to establish peptide-specific CTL lines in one of seven donors by incubating PBMCs with HPV-16 E7(11-20) peptide. When we employed autologous peptide-pulsed dendritic cells to stimulate CD8+ cell-enriched PBMCs, we obtained CTL lines in four of seven donors. The primed CTLs were able to lyse the HLA-A2+ and HPV-16+ cervical cancer cell line Caski. SiHa, an HLA-A2-, but HPV 16+, cervical cancer cell line could be lysed only after transfection with HLA-A2. In addition, a high cytotoxicity (>80%) was obtained against peptide-pulsed, but not unpulsed, targets such as autologous Ebstein-Barr virus-immortalized B cells or allogeneic lipopolysaccaride-stimulated PBMCs. DCs were clearly the most potent of all tested antigen presenting cells to stimulate a CTL response in a proliferation assay. CONCLUSION: HPV-16 E7 peptide-specific CTLs could be generated in vitro. A practical protocol to expand the CTLs to a sufficient number for an application in a clinical trial is in progress.
- Find related publications in this database (using NLM MeSH Indexing)
- Dendritic Cells - immunology
- Female - immunology
- Humans - immunology
- Immunotherapy - methods
- Oncogene Proteins, Viral - immunology
- Papillomaviridae - immunology
- Species Specificity - immunology
- T-Lymphocytes, Cytotoxic - immunology
- Tumor Cells, Cultured - immunology
- Uterine Cervical Neoplasms - therapy