Interleukin-12-secreting human papillomavirus type 16-transformed cells provide a potent cancer vaccine that generates E7-directed immunity
| Autor: | Sophie Hallez, Thomas F. Gajewski, Kris Thielemans, Christina Giannouli, Arsène Burny, Oberdan Leo, Odile Detremmerie |
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| Přispěvatelé: | Physiology, Laboratory of Molecullar and Cellular Therapy |
| Rok vydání: | 1999 |
| Předmět: |
Cancer Research
medicine.medical_treatment Papillomavirus E7 Proteins Genes myc Biology Cancer Vaccines Virus Interferon-gamma Mice Immune system Immunity Antigens CD medicine Animals Papillomavirus Vaccines Papillomaviridae Cell Line Transformed Mice Inbred BALB C Membrane Glycoproteins Cancer Immunotherapy Oncogene Proteins Viral Th1 Cells medicine.disease Interleukin-12 Cytokine Oncology Immunology Interleukin 12 Cancer research B7-1 Antigen Female Cancer vaccine B7-2 Antigen |
| Zdroj: | International journal of cancer. 81(3) |
| ISSN: | 0020-7136 |
| Popis: | The development of a vaccine that would be capable of preventing or curing the (pre)cancerous lesions induced by genital oncogenic human papillomaviruses (HPVs) is the focus of much research. Many studies are presently evaluating vaccines based on the viral E6 and E7 oncoproteins, both of which are continually expressed by tumor cells. The success of a cancer vaccine relies, in large part, on the induction of a tumor-specific Th1-type immunity. In this study, we have evaluated the ability of B7-related and/or interleukin-12 (IL-12)-expressing, non-immunogenic murine HPV16-transformed BMK-16/myc cells, to achieve this goal. BMK-16/myc cells engineered to express surface B7–1 or B7–2 molecules remain tumorigenic in syngeneic BALB/c mice, suggesting that expression of these molecules alone is not sufficient to induce tumor regression. In contrast, mice injected with tumor cells engineered to secrete IL-12 remained tumor-free, demonstrating that IL-12 expression is sufficient to induce tumor rejection. IL-12-secreting BMK-16/myc cells were further shown to induce potent and specific long-term tumor resistance, even after irradiation. B7–1 was found to slightly but systematically improve anti-tumor immunity elicited by IL-12-secreting BMK-16/myc cells. Injection of irradiated B7–1/IL-12+ BMK-16/myc cells generates long-lasting, Th1-type, BMK-16/myc-directed immunity in tumor-resistant mice. These mice display a memory-type, E7-specific, cell-mediated immune response, which is potentially significant for clinical applications. Int. J. Cancer 81:428–437, 1999. © 1999 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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