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Incomplete tumour control following DNA vaccination against rat gliomas expressing a model antigen
Please always quote using this URN: urn:nbn:de:bvb:20-opus-126775
- Background Vaccination against tumour-associated antigens is one approach to elicit anti-tumour responses. We investigated the effect of polynucleotide (DNA) vaccination using a model antigen (E. coli lacZ) in a syngeneic gliosarcoma model (9L). Methods Fisher 344 rats were vaccinated thrice by intramuscular injection of a lacZ-encoding or a control plasmid in weekly intervals. One week after the last vaccination, lacZ-expressing 9L cells were implanted into the striatum. Results After 3 weeks, in lacZ-vaccinated animals the tumoursBackground Vaccination against tumour-associated antigens is one approach to elicit anti-tumour responses. We investigated the effect of polynucleotide (DNA) vaccination using a model antigen (E. coli lacZ) in a syngeneic gliosarcoma model (9L). Methods Fisher 344 rats were vaccinated thrice by intramuscular injection of a lacZ-encoding or a control plasmid in weekly intervals. One week after the last vaccination, lacZ-expressing 9L cells were implanted into the striatum. Results After 3 weeks, in lacZ-vaccinated animals the tumours were significantly smaller than in control-vaccinated animals. In cytotoxic T cell assays lysis rates of >50 % could only be observed in a few of the lacZ-vaccinated animals. This response was directed against lacZ-expressing and parental 9L cells but not against syngeneic MADB 106 adenocarcinoma cells. In Elispot assays interferon-γ production was observed upon stimulation with 9LlacZ and 9L wild-type but not MADB 106 cells. This response was higher for lacZ-immunized animals. All animals revealed dense infiltrates with CD8+ lymphocytes and, to a lesser extent, with NK cells. CD25-staining indicated cells possibly associated with the maintenance of peripheral tolerance to self-antigens. All tumours were densely infiltrated by microglia consisting mostly of ramified cells. Only focal accumulation of macrophage-like cells expressing ED1, a marker for phagocytic activity, was observed. Conclusion Prophylactic DNA vaccination resulted in effective but incomplete suppression of brain tumour formation. Mechanisms other than cytotoxic T cell responses as measured in the generally used in vitro assays appear to play a role in tumour suppression.…
Author: | Christian Ginzkey, Sven Eicker, Matthias Marget, Jörg Krause, Stefan Brecht, Manfred Westphal, Heinz-Hermann Hugo, Maximilian Mehdorn, Jörg Steinmann, Wolfgang Hamel |
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URN: | urn:nbn:de:bvb:20-opus-126775 |
Document Type: | Journal article |
Faculties: | Medizinische Fakultät / Klinik und Poliklinik für Hals-, Nasen- und Ohrenkrankheiten, plastische und ästhetische Operationen |
Language: | English |
Parent Title (English): | Acta Neurochirurgica |
Year of Completion: | 2013 |
Volume: | 155 |
Issue: | 1 |
Pagenumber: | 51-59 |
Source: | Acta Neurochirurgica (2013) 155:51–59 DOI 10.1007/s00701-012-1526-7 |
DOI: | https://doi.org/10.1007/s00701-012-1526-7 |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Tag: | DNA vaccination; immunotherapy; lacZ; rat glioma |
Release Date: | 2016/02/09 |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung |