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dc.contributor.authorPohla, Heike
dc.contributor.authorBuchner, Alexander
dc.contributor.authorStadlbauer, Birgit
dc.contributor.authorFrankenberger, Bernhard
dc.contributor.authorStevanovic, Stefan
dc.contributor.authorWalter, Steffen
dc.contributor.authorFrank, Ronald
dc.contributor.authorSchwachula, Tim
dc.contributor.authorOlek, Sven
dc.contributor.authorKopp, Joachim
dc.contributor.authorWillimsky, Gerald
dc.contributor.authorStief, Christian G
dc.contributor.authorHofstetter, Alfons
dc.contributor.authorPezzutto, Antonio
dc.contributor.authorBlankenstein, Thomas
dc.contributor.authorOberneder, Ralph
dc.contributor.authorSchendel, Dolores J
dc.date.accessioned2017-02-16T15:29:53Z
dc.date.available2017-02-16T15:29:53Z
dc.date.issued2013-02-08
dc.identifier.citationHigh immune response rates and decreased frequencies of regulatory T cells in metastatic renal cell carcinoma patients after tumor cell vaccination. 2013, 18:1499-508 Mol. Med.en
dc.identifier.issn1528-3658
dc.identifier.pmid23269976
dc.identifier.doi10.2119/molmed.2012.00221
dc.identifier.urihttp://hdl.handle.net/10033/620827
dc.description.abstractOur previously reported phase I clinical trial with the allogeneic gene-modified tumor cell line RCC-26/CD80/IL-2 showed that vaccination was well tolerated and feasible in metastatic renal cell carcinoma (RCC) patients. Substantial disease stabilization was observed in most patients despite a high tumor burden at study entry. To investigate alterations in immune responses that might contribute to this effect, we performed an extended immune monitoring that included analysis of reactivity against multiple antigens, cytokine/chemokine changes in serum and determination of the frequencies of immune suppressor cell populations, including natural regulatory T cells (nTregs) and myeloid-derived suppressor cell subsets (MDSCs). An overall immune response capacity to virus-derived control peptides was present in 100% of patients before vaccination. Vaccine-induced immune responses to tumor-associated antigens occurred in 75% of patients, demonstrating the potent immune stimulatory capacity of this generic vaccine. Furthermore, some patients reacted to peptide epitopes of antigens not expressed by the vaccine, showing that epitope-spreading occurred in vivo. Frequencies of nTregs and MDSCs were comparable to healthy donors at the beginning of study. A significant decrease of nTregs was detected after vaccination (p = 0.012). High immune response rates, decreased frequencies of nTregs and a mixed T helper 1/T helper 2 (T(H)1/T(H)2)-like cytokine pattern support the applicability of this RCC generic vaccine for use in combination therapies.
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshCancer Vaccinesen
dc.subject.meshCarcinoma, Renal Cellen
dc.subject.meshCytokinesen
dc.subject.meshHumansen
dc.subject.meshImmunityen
dc.subject.meshKidney Neoplasmsen
dc.subject.meshLymphocyte Counten
dc.subject.meshLymphocytes, Tumor-Infiltratingen
dc.subject.meshMyeloid Cellsen
dc.subject.meshNeoplasm Metastasisen
dc.subject.meshNeoplasm Stagingen
dc.subject.meshPeptidesen
dc.subject.meshSurvival Analysisen
dc.subject.meshT-Lymphocytes, Regulatoryen
dc.subject.meshTh1 Cellsen
dc.subject.meshTh2 Cellsen
dc.subject.meshTime Factorsen
dc.subject.meshTreatment Outcomeen
dc.subject.meshVaccinationen
dc.titleHigh immune response rates and decreased frequencies of regulatory T cells in metastatic renal cell carcinoma patients after tumor cell vaccination.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalMolecular medicine (Cambridge, Mass.)en
refterms.dateFOA2018-06-13T15:57:07Z
html.description.abstractOur previously reported phase I clinical trial with the allogeneic gene-modified tumor cell line RCC-26/CD80/IL-2 showed that vaccination was well tolerated and feasible in metastatic renal cell carcinoma (RCC) patients. Substantial disease stabilization was observed in most patients despite a high tumor burden at study entry. To investigate alterations in immune responses that might contribute to this effect, we performed an extended immune monitoring that included analysis of reactivity against multiple antigens, cytokine/chemokine changes in serum and determination of the frequencies of immune suppressor cell populations, including natural regulatory T cells (nTregs) and myeloid-derived suppressor cell subsets (MDSCs). An overall immune response capacity to virus-derived control peptides was present in 100% of patients before vaccination. Vaccine-induced immune responses to tumor-associated antigens occurred in 75% of patients, demonstrating the potent immune stimulatory capacity of this generic vaccine. Furthermore, some patients reacted to peptide epitopes of antigens not expressed by the vaccine, showing that epitope-spreading occurred in vivo. Frequencies of nTregs and MDSCs were comparable to healthy donors at the beginning of study. A significant decrease of nTregs was detected after vaccination (p = 0.012). High immune response rates, decreased frequencies of nTregs and a mixed T helper 1/T helper 2 (T(H)1/T(H)2)-like cytokine pattern support the applicability of this RCC generic vaccine for use in combination therapies.


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