Publikationen

Human Gene Therapy 21 (3): 285-297 (2010-03)

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 I trial of an allogeneic gene-modified tumor cell vaccine (RCC-26/CD80/IL-2) in patients with metastatic renal cell carcinoma

Description:
Aims: Pre-clinical 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 I vaccine trial of renal cell carcinoma patients with metastatic disease (mRCC). Fifteen patients of 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 106 cells over 22 weeks. Primary study parameters were safety and toxicity. Sequential blood samples were analyzed by interferon-gamma-ELISPOT assays to detect tumor antigen-associated (TAA) effector cells. Results: 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 (DTH) 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 over-expressed TAA were detected in 9 of 12 evaluated patients. No tumor regressions occurred according to RECIST criteria, however median time to progression was 5.3 months and median survival was 15.6 months, indicating substantial disease stabilization. Conclusions: 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 TAA in the majority of study participants. These results suggest that this vaccine could be useful in combination therapies and/or minimal residual disease.

Keywords: CD80 Antigens, Neoplasm Antigens, Western Blotting, Bone Neoplasms, Cancer Vaccines, Renal Cell Carcinoma, Feasibility Studies, Gene Expression Profiling, HLA-A Antigens, Delayed Hypersensitivity, Immunoenzyme Techniques, Recombinant Interferon-gamma, Interleukin-2, Kidney Neoplasms, Lung Neoplasms, Lymphocyte Activation, Oligonucleotide Array Sequence Analysis, Messenger RNA, Reverse Transcriptase Polymerase Chain Reaction, T-Lymphocytes, Biological Tumor Markers, Vaccination

Type: Article

PubMed: 19788391
Official URL: https://doi.org/10.1089/hum.2008.192
MDC Repository: https://edoc.mdc-berlin.de/10508/