PuSH - Publication Server of Helmholtz Zentrum München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
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.*

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.

Gene Ther. 18, 354-363 (2011)
Publ. Version/Full Text DOI PMC
Closed
Open Access Green as soon as Postprint is submitted to ZB.
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.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
4.538
1.109
9
17
Tags
Annotations
Special Publikation
Hide on homepage

Edit extra information
Edit own tags
Private
Edit own annotation
Private
Hide on publication lists
on hompage
Mark as special
publikation
Publication type Article: Journal article
Document type Scientific Article
Keywords allogeneic vaccine; renal cell carcinoma; gene transfer; tumor vaccination
Language english
Publication Year 2011
HGF-reported in Year 2011
ISSN (print) / ISBN 0969-7128
e-ISSN 1476-5462
Journal Gene Therapy
Quellenangaben Volume: 18, Issue: 4, Pages: 354-363 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Reviewing status Peer reviewed
Institute(s) Institute of Molecular Immunology (IMI)
CCG Immune Monitoring (Platform) (IMI-KIM)
POF-Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s) Immune Response and Infection
PSP Element(s) G-501700-001
G-501700-002
G-520400-001
G-501790-001
G-501790-002
G-501790-003
PubMed ID 21068778
DOI 10.1038/gt.2010.143
Scopus ID 79953787845
Erfassungsdatum 2011-07-22
[➜Report correction]