High immune response rates and decreased frequencies of regulatory T cells in metastatic renal cell carcinoma patients after tumor cell vaccination.

2.50
Hdl Handle:
http://hdl.handle.net/10033/620827
Title:
High immune response rates and decreased frequencies of regulatory T cells in metastatic renal cell carcinoma patients after tumor cell vaccination.
Authors:
Pohla, Heike; Buchner, Alexander; Stadlbauer, Birgit; Frankenberger, Bernhard; Stevanovic, Stefan; Walter, Steffen; Frank, Ronald ( 0000-0003-2683-6511 ) ; Schwachula, Tim; Olek, Sven; Kopp, Joachim; Willimsky, Gerald; Stief, Christian G; Hofstetter, Alfons; Pezzutto, Antonio; Blankenstein, Thomas; Oberneder, Ralph; Schendel, Dolores J
Abstract:
Our 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.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Citation:
High 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.
Journal:
Molecular medicine (Cambridge, Mass.)
Issue Date:
8-Feb-2013
URI:
http://hdl.handle.net/10033/620827
DOI:
10.2119/molmed.2012.00221
PubMed ID:
23269976
Type:
Article
Language:
en
ISSN:
1528-3658
Appears in Collections:
Publications of the research group Chemical Biology (CBIO)

Full metadata record

DC FieldValue Language
dc.contributor.authorPohla, Heikeen
dc.contributor.authorBuchner, Alexanderen
dc.contributor.authorStadlbauer, Birgiten
dc.contributor.authorFrankenberger, Bernharden
dc.contributor.authorStevanovic, Stefanen
dc.contributor.authorWalter, Steffenen
dc.contributor.authorFrank, Ronalden
dc.contributor.authorSchwachula, Timen
dc.contributor.authorOlek, Svenen
dc.contributor.authorKopp, Joachimen
dc.contributor.authorWillimsky, Geralden
dc.contributor.authorStief, Christian Gen
dc.contributor.authorHofstetter, Alfonsen
dc.contributor.authorPezzutto, Antonioen
dc.contributor.authorBlankenstein, Thomasen
dc.contributor.authorOberneder, Ralphen
dc.contributor.authorSchendel, Dolores Jen
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.en
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

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