Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

High immune response rates and decreased frequencies of regulatory T cells in metastatic renal cell carcinoma patients after tumor cell vaccination

[img] PDF - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
633kB

Item Type:Article
Title:High immune response rates and decreased frequencies of regulatory T cells in metastatic renal cell carcinoma patients after tumor cell vaccination
Creators Name:Pohla, H. and Buchner, A. and Stadlbauer, B. and Frankenberger, B. and Stevanovic, S. and Walter, S. and Frank, R. and Schwachula, T. and Olek, S. and Kopp, J. and Willimsky, G. and Stief, C.G. and Hofstetter, A. and Pezzutto, A. and Blankenstein, T. and Oberneder, R. and Schendel, D.J.
Abstract:Our previously reported phase I clinical trial with the allogeneic gene-modified tumor cell line RCC-26/CD80/IL-2 showed that vaccination was well-tolerated and feasible in metastatic renal cell carcinoma (mRCC) patients. Substantial disease stabilization was observed in most patients despite a high tumor burden at study entry. To investigate alterations in immune responses that might contribute to this effect, we performed an extended immune monitoring that included analysis of reactivity against multiple antigens, cytokine/chemokine changes in serum, and determination of the frequencies of immune suppressor cell populations, including natural regulatory T cells (nTregs) and myeloid-derived suppressor cell subsets (MDSCs). An overall immune response capacity to virus-derived control peptides was present in 100% of patients before vaccination. Vaccine-induced immune responses to tumor-associated antigens (TAAs) occurred in 75% of patients, demonstrating the potent immune stimulatory capacity of this generic vaccine. Furthermore, some patients reacted to peptide epitopes of antigens not expressed by the vaccine, showing that epitope-spreading occurred in vivo. Frequencies of nTregs and MDSCs were comparable to healthy donors at study begin. A significant decrease of nTregs was detected following vaccination (p=0.012). High immune response rates, decreased frequencies of nTregs, and a mixed T(H)1/T(H)2-like cytokine pattern support the applicability of this RCC generic vaccine for use in combination therapies.
Keywords:Kidney Cancer, Immunotherapy, Immune Monitoring, Regulatory T Cell, Myeloid-Derived Suppressor Cell
Source:Molecular Medicine
ISSN:1076-1551
Publisher:Feinstein Institute for Medical Research (U.S.A.)
Volume:18
Page Range:1499-1508
Date:8 February 2013
Official Publication:https://doi.org/10.2119/molmed.2012.00221
PubMed:View item in PubMed

Repository Staff Only: item control page

Downloads

Downloads per month over past year

Open Access
MDC Library