PMID- 15365776
OWN - NLM
STAT- MEDLINE
DCOM- 20050203
LR  - 20240426
IS  - 0340-7004 (Print)
IS  - 1432-0851 (Electronic)
IS  - 0340-7004 (Linking)
VI  - 54
IP  - 2
DP  - 2005 Feb
TI  - A CD80-transfected human breast cancer cell variant induces HER-2/neu-specific T 
      cells in HLA-A*02-matched situations in vitro as well as in vivo.
PG  - 129-40
AB  - Adjuvant treatment is still only working in a small percentage of breast cancer 
      patients. Therefore, new strategies need to be developed. Immunotherapies are a 
      very promising approach because they could successfully attack tumor cells in the 
      stage of dormancy. To assess the feasibility of using an allogeneic approach for 
      vaccination of breast cancer patients, we selected a CD80-transfected breast 
      cancer cell line based on its immunogenic properties. Using CD80+ KS breast 
      cancer cells and human leukocyte antigen (HLA)-A*02-matched peripheral blood 
      mononuclear cells (PBMCs) of breast cancer patients in allogeneic mixed 
      lymphocyte-tumor cell cultures (MLTCs), it was possible to isolate 
      HLA-A*02-restricted cytotoxic T cells (CTLs). Furthermore, a genetically modified 
      KS variant expressing influenza A matrix protein serving as a surrogate 
      tumor-associated antigen (TAA) was able to stimulate flu peptide-specific T cells 
      alongside the induction of alloresponses in MLTCs. KS breast cancer cells were 
      demonstrated to express already known TAAs such as CEA, MUC-1, MAGE-1, MAGE-2, 
      and MAGE-3. To further improve antigenicity, HER-2/neu was added to this panel as 
      a marker antigen known to elicit HLA-A*02-restricted CTLs in patients with breast 
      cancer. Thus, the antigen-processing and antigen-presentation capacity of KS 
      cells was further demonstrated by the stimulation of HER-2/neu-specific CD8+ T 
      cells in PBMCs of breast cancer patients in vitro. These results gave a good 
      rationale for a phase I/II trial, where the CD80+ HER-2/neu-overexpressing KS 
      variant is actually used as a cellular vaccine in patients with metastatic breast 
      cancer. As a proof of principle, we present data from two patients where a 
      significant increase of interferon-gamma (IFN-gamma) release was detected when 
      postvaccination PBMCs were stimulated by allogeneic vaccine cells as well as by 
      HLA-A*02-restricted HER-2/neu epitopes. In whole cell vaccine trials, monitoring 
      is particularly challenging because of strong alloresponses and limited knowledge 
      of TAAs. In this study, a panel of HER-2/neu epitopes, together with the 
      quantitative real time (qRT)-PCR method to analyze vaccine-induced cytokines 
      secreted by T cells, proved to be highly sensitive and feasible to perform an 
      "immunological staging" following vaccination.
FAU - Guckel, Brigitte
AU  - Guckel B
AD  - Department of Gynecology and Obstetrics, University of Tubingen, Calwerstrasse 7, 
      72076, Tubingen, Germany. brigitte.gueckel@uni-tuebingen.de
FAU - Stumm, Susanne
AU  - Stumm S
FAU - Rentzsch, Christine
AU  - Rentzsch C
FAU - Marme, Alexander
AU  - Marme A
FAU - Mannhardt, Geeske
AU  - Mannhardt G
FAU - Wallwiener, Diethelm
AU  - Wallwiener D
LA  - eng
PT  - Clinical Trial
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20040909
PL  - Germany
TA  - Cancer Immunol Immunother
JT  - Cancer immunology, immunotherapy : CII
JID - 8605732
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (B7-1 Antigen)
RN  - 0 (Carcinoembryonic Antigen)
RN  - 0 (Cytokines)
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-A*02:01 antigen)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (MAGEA1 protein, human)
RN  - 0 (MAGEA3 protein, human)
RN  - 0 (Melanoma-Specific Antigens)
RN  - 0 (Mucin-1)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Viral Matrix Proteins)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Antigens, Neoplasm/metabolism
MH  - B7-1 Antigen/immunology/*metabolism
MH  - Breast Neoplasms/*immunology/metabolism/pathology
MH  - Carcinoembryonic Antigen/metabolism
MH  - Cytokines/metabolism
MH  - Feasibility Studies
MH  - Female
MH  - HLA-A Antigens/*immunology
MH  - HLA-A2 Antigen
MH  - Humans
MH  - In Vitro Techniques
MH  - Influenza A virus/physiology
MH  - K562 Cells
MH  - Leukocytes, Mononuclear/immunology
MH  - Melanoma-Specific Antigens
MH  - Mucin-1/metabolism
MH  - Neoplasm Proteins/metabolism
MH  - Receptor, ErbB-2/genetics/immunology/*metabolism
MH  - T-Lymphocytes/*immunology/metabolism/pathology
MH  - T-Lymphocytes, Cytotoxic/*immunology
MH  - Transfection
MH  - Vaccination
MH  - Viral Matrix Proteins/metabolism
PMC - PMC11034349
EDAT- 2004/09/15 05:00
MHDA- 2005/02/04 09:00
PMCR- 2004/09/09
CRDT- 2004/09/15 05:00
PHST- 2004/03/22 00:00 [received]
PHST- 2004/06/14 00:00 [accepted]
PHST- 2004/09/15 05:00 [pubmed]
PHST- 2005/02/04 09:00 [medline]
PHST- 2004/09/15 05:00 [entrez]
PHST- 2004/09/09 00:00 [pmc-release]
AID - 583 [pii]
AID - 10.1007/s00262-004-0583-z [doi]
PST - ppublish
SO  - Cancer Immunol Immunother. 2005 Feb;54(2):129-40. doi: 10.1007/s00262-004-0583-z. 
      Epub 2004 Sep 9.