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dc.contributor.authorWestermann, J
dc.contributor.authorFlörcken, A
dc.contributor.authorWillimsky, G
dc.contributor.authorvan Lessen, A
dc.contributor.authorKopp, J
dc.contributor.authorTakvorian, A
dc.contributor.authorJöhrens, K
dc.contributor.authorLukowsky, A
dc.contributor.authorSchönemann, C
dc.contributor.authorSawitzki, B
dc.contributor.authorPohla, H
dc.contributor.authorFrank, Ronald
dc.contributor.authorDörken, B
dc.contributor.authorSchendel, D J
dc.contributor.authorBlankenstein, T
dc.contributor.authorPezzutto, A
dc.date.accessioned2017-02-16T14:26:51Z
dc.date.available2017-02-16T14:26:51Z
dc.date.issued2011-04
dc.identifier.citationAllogeneic gene-modified tumor cells (RCC-26/IL-7/CD80) as a vaccine in patients with metastatic renal cell cancer: a clinical phase-I study. 2011, 18 (4):354-63 Gene Ther.en
dc.identifier.issn1476-5462
dc.identifier.pmid21068778
dc.identifier.doi10.1038/gt.2010.143
dc.identifier.urihttp://hdl.handle.net/10033/620823
dc.description.abstractDespite novel targeted agents, prognosis of metastatic renal cell cancer (RCC) remains poor, and experimental therapeutic strategies are warranted. Transfection of tumor cells with co-stimulatory molecules and/or cytokines is able to increase immunogenicity. Therefore, in our clinical study, 10 human leukocyte antigen (HLA)-A(*)0201(+) patients with histologically-confirmed progressive metastatic clear cell RCC were immunized repetitively over 22 weeks with 2.5-40 × 10(6) interleukin (IL)-7/CD80 cotransfected allogeneic HLA-A(*)0201(+) tumor cells (RCC26/IL-7/CD80). Endpoints of the study were feasibility, safety, immunological and clinical responses. Vaccination was feasible and safe. In all, 50% of the patients showed stable disease throughout the study; the median time to progression was 18 weeks. However, vaccination with allogeneic RCC26/IL-7/CD80 tumor cells was not able to induce TH1-polarized immune responses. A TH2 cytokine profile with increasing amounts of antigen-specific IL-10 secretion was observed in most of the responding patients. Interferon-γ secretion by patient lymphocytes upon antigen-specific and non-specific stimulation was substantially impaired, both before and during vaccination, as compared with healthy controls. This is possibly due to profound tumor-induced immunosuppression, which may prevent induction of antitumor immune responses by the gene-modified vaccine. Vaccination in minimal residual disease with concurrent depletion of regulatory cells might be one strategy to overcome this limitation.
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshAdulten
dc.subject.meshAgeden
dc.subject.meshAntigens, CD80en
dc.subject.meshCancer Vaccinesen
dc.subject.meshCarcinoma, Renal Cellen
dc.subject.meshCell Line, Tumoren
dc.subject.meshFemaleen
dc.subject.meshHLA Antigensen
dc.subject.meshHumansen
dc.subject.meshInterleukin-7en
dc.subject.meshKidney Neoplasmsen
dc.subject.meshMaleen
dc.subject.meshMiddle Ageden
dc.subject.meshT-Lymphocytesen
dc.subject.meshTransfectionen
dc.titleAllogeneic gene-modified tumor cells (RCC-26/IL-7/CD80) as a vaccine in patients with metastatic renal cell cancer: a clinical phase-I study.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalGene therapyen
refterms.dateFOA2018-06-12T23:15:29Z
html.description.abstractDespite novel targeted agents, prognosis of metastatic renal cell cancer (RCC) remains poor, and experimental therapeutic strategies are warranted. Transfection of tumor cells with co-stimulatory molecules and/or cytokines is able to increase immunogenicity. Therefore, in our clinical study, 10 human leukocyte antigen (HLA)-A(*)0201(+) patients with histologically-confirmed progressive metastatic clear cell RCC were immunized repetitively over 22 weeks with 2.5-40 × 10(6) interleukin (IL)-7/CD80 cotransfected allogeneic HLA-A(*)0201(+) tumor cells (RCC26/IL-7/CD80). Endpoints of the study were feasibility, safety, immunological and clinical responses. Vaccination was feasible and safe. In all, 50% of the patients showed stable disease throughout the study; the median time to progression was 18 weeks. However, vaccination with allogeneic RCC26/IL-7/CD80 tumor cells was not able to induce TH1-polarized immune responses. A TH2 cytokine profile with increasing amounts of antigen-specific IL-10 secretion was observed in most of the responding patients. Interferon-γ secretion by patient lymphocytes upon antigen-specific and non-specific stimulation was substantially impaired, both before and during vaccination, as compared with healthy controls. This is possibly due to profound tumor-induced immunosuppression, which may prevent induction of antitumor immune responses by the gene-modified vaccine. Vaccination in minimal residual disease with concurrent depletion of regulatory cells might be one strategy to overcome this limitation.


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