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.
dc.contributor.author | Westermann, J | |
dc.contributor.author | Flörcken, A | |
dc.contributor.author | Willimsky, G | |
dc.contributor.author | van Lessen, A | |
dc.contributor.author | Kopp, J | |
dc.contributor.author | Takvorian, A | |
dc.contributor.author | Jöhrens, K | |
dc.contributor.author | Lukowsky, A | |
dc.contributor.author | Schönemann, C | |
dc.contributor.author | Sawitzki, B | |
dc.contributor.author | Pohla, H | |
dc.contributor.author | Frank, Ronald | |
dc.contributor.author | Dörken, B | |
dc.contributor.author | Schendel, D J | |
dc.contributor.author | Blankenstein, T | |
dc.contributor.author | Pezzutto, A | |
dc.date.accessioned | 2017-02-16T14:26:51Z | |
dc.date.available | 2017-02-16T14:26:51Z | |
dc.date.issued | 2011-04 | |
dc.identifier.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. | en |
dc.identifier.issn | 1476-5462 | |
dc.identifier.pmid | 21068778 | |
dc.identifier.doi | 10.1038/gt.2010.143 | |
dc.identifier.uri | http://hdl.handle.net/10033/620823 | |
dc.description.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. | |
dc.language.iso | en | en |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | * |
dc.subject.mesh | Adult | en |
dc.subject.mesh | Aged | en |
dc.subject.mesh | Antigens, CD80 | en |
dc.subject.mesh | Cancer Vaccines | en |
dc.subject.mesh | Carcinoma, Renal Cell | en |
dc.subject.mesh | Cell Line, Tumor | en |
dc.subject.mesh | Female | en |
dc.subject.mesh | HLA Antigens | en |
dc.subject.mesh | Humans | en |
dc.subject.mesh | Interleukin-7 | en |
dc.subject.mesh | Kidney Neoplasms | en |
dc.subject.mesh | Male | en |
dc.subject.mesh | Middle Aged | en |
dc.subject.mesh | T-Lymphocytes | en |
dc.subject.mesh | Transfection | en |
dc.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. | en |
dc.type | Article | en |
dc.contributor.department | Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. | en |
dc.identifier.journal | Gene therapy | en |
refterms.dateFOA | 2018-06-12T23:15:29Z | |
html.description.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. |