Allogeneic gene-modified tumor cells (RCC-26/IL-7/CD80) as a vaccine in patients with metastatic renal cell cancer: a clinical phase-I study.

2.50
HDL Handle:
http://hdl.handle.net/10033/201240
Title:
Allogeneic gene-modified tumor cells (RCC-26/IL-7/CD80) as a vaccine in patients with metastatic renal cell cancer: a clinical phase-I study.
Authors:
Westermann, J; Flörcken, A; Willimsky, G; van Lessen, A; Kopp, J; Takvorian, A; Jöhrens, K; Lukowsky, A; Schönemann, C; Sawitzki, B; Pohla, H; Frank, R; Dörken, B; Schendel, D J; Blankenstein, T; Pezzutto, A
Abstract:
Despite 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.
Affiliation:
Department of Hematology, Oncology and Tumor Immunology, Charité-University Medicine Berlin, Campus Virchow-Klinikum and Campus Berlin-Buch, Berlin, Germany. joerg.westermann@charite.de
Citation:
Allogeneic 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.
Journal:
Gene therapy
Issue Date:
Apr-2011
URI:
http://hdl.handle.net/10033/201240
DOI:
10.1038/gt.2010.143
PubMed ID:
21068778
Type:
Article
Language:
en
ISSN:
1476-5462
Appears in Collections:
Publications of Dept. Chemical Biology (CBIO)

Full metadata record

DC FieldValueLanguage
dc.contributor.authorWestermann, Jen
dc.contributor.authorFlörcken, Aen
dc.contributor.authorWillimsky, Gen
dc.contributor.authorvan Lessen, Aen
dc.contributor.authorKopp, Jen
dc.contributor.authorTakvorian, Aen
dc.contributor.authorJöhrens, Ken
dc.contributor.authorLukowsky, Aen
dc.contributor.authorSchönemann, Cen
dc.contributor.authorSawitzki, Ben
dc.contributor.authorPohla, Hen
dc.contributor.authorFrank, Ren
dc.contributor.authorDörken, Ben
dc.contributor.authorSchendel, D Jen
dc.contributor.authorBlankenstein, Ten
dc.contributor.authorPezzutto, Aen
dc.date.accessioned2012-01-10T12:17:51Z-
dc.date.available2012-01-10T12:17:51Z-
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/10033/201240-
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.en
dc.language.isoenen
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.departmentDepartment of Hematology, Oncology and Tumor Immunology, Charité-University Medicine Berlin, Campus Virchow-Klinikum and Campus Berlin-Buch, Berlin, Germany. joerg.westermann@charite.deen
dc.identifier.journalGene therapyen

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