TY  - JOUR
A1  - Ginzkey, Christian
A1  - Eicker, Sven
A1  - Marget, Matthias
A1  - Krause, Jörg
A1  - Brecht, Stefan
A1  - Westphal, Manfred
A1  - Hugo, Heinz-Hermann
A1  - Mehdorn, Maximilian
A1  - Steinmann, Jörg
A1  - Hamel, Wolfgang
T1  - Incomplete tumour control following DNA vaccination against rat gliomas expressing a model antigen
JF  - Acta Neurochirurgica
N2  - 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 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.
KW  - lacZ
KW  - rat glioma
KW  - immunotherapy
KW  - DNA vaccination
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-126775
VL  - 155
IS  - 1
ER  - 
TY  - JOUR
A1  - Banas, Bernhard
A1  - Steubl, Dominik
A1  - Renders, Lutz
A1  - Chittka, Dominik
A1  - Banas, Miriam C.
A1  - Wekerle, Thomas
A1  - Koch, Martina
A1  - Witzke, Oliver
A1  - Mühlfeld, Anja
A1  - Sommerer, Claudia
A1  - Habicht, Antje
A1  - Hugo, Christian
A1  - Hünig, Thomas
A1  - Lindemann, Monika
A1  - Schmidt, Traudel
A1  - Rascle, Anne
A1  - Barabas, Sascha
A1  - Deml, Ludwig
A1  - Wagner, Ralf
A1  - Krämer, Bernhard K.
A1  - Krüger, Bernd
T1  - Clinical validation of a novel enzyme-linked immunosorbent spot assay-based in vitro diagnostic assay to monitor cytomegalovirus-specific cell-mediated immunity in kidney transplant recipients: a multicenter, longitudinal, prospective, observational study
JF  - Transplant International
N2  - Impaired cytomegalovirus (CMV)-specific cell-mediated immunity (CMV-CMI) is a major cause of CMV reactivation and associated complications in solid-organ transplantation. Reliably assessing CMV-CMI is desirable to individually adjust antiviral and immunosuppressive therapy. This study aimed to evaluate the suitability of T-Track® CMV, a novel IFN-γ ELISpot assay based on the stimulation of peripheral blood mononuclear cells with pp65 and IE-I CMV proteins, to monitor CMV-CMI following kidney transplantation. A prospective longitudinal multicenter study was conducted in 86 intermediate-risk renal transplant recipients. CMV-CMI, CMV viral load, and clinical complications were monitored over 6 months post-transplantation. Ninety-five percent and 88–92% ELISpot assays were positive pre- and post-transplantation, respectively. CMV-specific response was reduced following immunosuppressive treatment and increased in patients with graft rejection, indicating the ability of the ELISpot assay to monitor patients' immunosuppressive state. Interestingly, median pp65-specific response was ninefold higher in patients with self-clearing viral load compared to antivirally treated patients prior to first viral load detection (P < 0.001), suggesting that reactivity to pp65 represents a potential immunocompetence marker. Altogether, T-Track® CMV is a highly sensitive IFN-γ ELISpot assay, suitable for the immunomonitoring of CMV-seropositive renal transplant recipients, and with a potential use for the risk assessment of CMV-related clinical complications (ClinicalTrials.gov Identifier: NCT02083042).
KW  - CMV-specific cell-mediated immunity
KW  - cytomegalovirus
KW  - IFN‐γ ELISpot
KW  - immunomonitoring
KW  - in vitro diagnostic
KW  - kidney or renal transplantation
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-221468
VL  - 31
ER  -