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Buchner, A.* ; Pohla, H. ; Willimsky, G.* ; Frankenberger, B. ; Frank, R. ; Baur-Melnyk, A.* ; Siebels, M.* ; Stief, C.G.* ; Hofstetter, A.* ; Kopp, J.* ; Pezzutto, A.* ; Blankenstein, T.* ; Oberneder, R.* ; Schendel, D.J.

Phase 1 trial of allogeneic gene-modified tumor cell vaccine RCC-26/CD80/IL-2 in patients with metastatic renal cell carcinoma.

Hum. Gene Ther. 21, 285-297 (2010)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Preclinical studies showed that the allogeneic tumor cell line RCC-26 displayed natural immunogenic potential that was enhanced through expression of CD80 costimulatory molecules and secretion of interleukin-2. Here we report the study of RCC-26/CD80/IL-2 cells in a phase 1 vaccine trial of renal cell carcinoma patients with metastatic disease (mRCC). Fifteen patients of the HLA-A*0201 allotype, with at least one metastatic lesion, were included. Irradiated vaccine cells were applied in increasing doses of 2.5, 10, and 40 x 10(6) cells over 22 weeks. Primary study parameters included safety and toxicity. Sequential blood samples were analyzed by interferon-gamma enzyme-linked immunospot assays to detect tumor antigen-associated (TAA) effector cells. The vaccine was well tolerated and the designated vaccination course was completed in 9 of 15 patients. Neither vaccine-induced autoimmunity nor systemic side effects were observed. Delayed-type hypersensitivity skin reactions were detected in 11 of 12 evaluated patients and were particularly strong in patients with prolonged survival. In parallel, vaccine-induced immune responses against vaccine or overexpressed TAA were detected in 9 of 12 evaluated patients. No tumor regressions occurred according to RECIST (Response Evaluation Criteria in Solid Tumors) criteria; however, median time to progression was 5.3 months and median survival was 15.6 months, indicating substantial disease stabilization. We conclude that vaccine use was safe and feasible in mRCC. Clinical benefits were limited in these patients with advanced disease; however, immune monitoring revealed vaccine-induced responses against multiple TAAs in the majority of study participants. These results suggest that this vaccine could be useful in combination therapies and/or minimal residual disease.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Cytotoxic T-lymphocytes; Infiltrating lymphocytes; Epithelial tumors; Mass-spectrometry; Cancer vaccines; Dendritic cells; Kidney cancer; Interleukin-2; Antigen; Identification
Language english
Publication Year 2010
HGF-reported in Year 2010
ISSN (print) / ISBN 1043-0342
e-ISSN 1557-7422
Journal Human Gene Therapy. Clinical Development
Quellenangaben Volume: 21, Issue: 3, Pages: 285-297 Article Number: , Supplement: ,
Publisher Mary Ann Liebert
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-501790-001
G-501700-005
G-520400-001
G-501700-002
PubMed ID 19788391
DOI 10.1089/hum.2008.192
Scopus ID 77949719412
Erfassungsdatum 2010-02-12
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