PMID- 17653857
OWN - NLM
STAT- MEDLINE
DCOM- 20080715
LR  - 20201215
IS  - 0167-6806 (Print)
IS  - 0167-6806 (Linking)
VI  - 109
IP  - 2
DP  - 2008 May
TI  - Generation of mammaglobin-A-specific CD4 T cells and identification of candidate 
      CD4 epitopes for breast cancer vaccine strategies.
PG  - 305-14
AB  - BACKGROUND: Mammaglobin-A (MGB) is a breast cancer-associated antigen that is an 
      attractive target for immune intervention. MGB has been shown to induce a 
      specific CD8 T cell response in breast cancer patients, but little is known about 
      a possible MGB-specific CD4 T cell response. METHODS: Peripheral blood-derived 
      CD4(+)CD25(-) T cells were stimulated in vitro with MGB-pulsed antigen-presenting 
      cells (APC). The MGB and human leukocyte antigen (HLA) class II specificity of 
      the CD4 T cell lines was confirmed by cytokine release following restimulation 
      with autologous and allogenic APC pulsed with MGB from different sources. 
      Candidate HLA class II-restricted epitopes were identified by computer algorithm 
      and validated in cytokine release assays. RESULTS: MGB-specific CD4 T cells were 
      successfully generated in cultures from six of seven donors. Restimulation of 
      MGB-specific CD4 T cells with MGB-pulsed APC induced significantly higher levels 
      of interferon (IFN)-gamma release than APC pulsed with an irrelevant protein (P = 
      0.0004). Cultures from five of seven donors showed a pure Th1 type response as 
      evidenced by the absence of interleukin (IL)-4. MGB-specific CD4 T cells 
      recognized both recombinant and naturally processed MGB presented by APC. This 
      recognition was HLA class II-restricted, as HLA-DR mismatched APC were not 
      recognized. MGB-specific CD4 T cells from three of four donors recognized 
      MGB-derived, HLA class II-restricted peptides pulsed onto APC. CONCLUSIONS: We 
      have successfully generated MGB-specific CD4 T cell cultures and identified 
      candidate MGB HLA class II epitopes. These studies should facilitate study of the 
      CD4 T cell response to MGB, and the development and monitoring of vaccine 
      strategies targeting this unique antigen.
FAU - Viehl, Carsten T
AU  - Viehl CT
AD  - Department of Surgery, Washington University School of Medicine, St. Louis, MO 
      63110, USA.
FAU - Frey, Daniel M
AU  - Frey DM
FAU - Phommaly, Chanpheng
AU  - Phommaly C
FAU - Chen, Tingting
AU  - Chen T
FAU - Fleming, Timothy P
AU  - Fleming TP
FAU - Gillanders, William E
AU  - Gillanders WE
FAU - Eberlein, Timothy J
AU  - Eberlein TJ
FAU - Goedegebuure, Peter S
AU  - Goedegebuure PS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070726
PL  - Netherlands
TA  - Breast Cancer Res Treat
JT  - Breast cancer research and treatment
JID - 8111104
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Mammaglobin A)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (SCGB2A2 protein, human)
RN  - 9060-09-7 (Uteroglobin)
SB  - IM
MH  - Antigen Presentation/immunology
MH  - Antigens, Neoplasm/immunology
MH  - Breast Neoplasms/*immunology
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - *Cancer Vaccines
MH  - Cell Line, Tumor
MH  - Epitopes, T-Lymphocyte/*immunology
MH  - Female
MH  - Histocompatibility Antigens Class II/immunology
MH  - Humans
MH  - Lymphocyte Activation/immunology
MH  - Mammaglobin A
MH  - Neoplasm Proteins/*immunology
MH  - Recombinant Proteins/immunology
MH  - Uteroglobin/*immunology
EDAT- 2007/07/27 09:00
MHDA- 2008/07/17 09:00
CRDT- 2007/07/27 09:00
PHST- 2007/03/02 00:00 [received]
PHST- 2007/06/11 00:00 [accepted]
PHST- 2007/07/27 09:00 [pubmed]
PHST- 2008/07/17 09:00 [medline]
PHST- 2007/07/27 09:00 [entrez]
AID - 10.1007/s10549-007-9657-x [doi]
PST - ppublish
SO  - Breast Cancer Res Treat. 2008 May;109(2):305-14. doi: 10.1007/s10549-007-9657-x. 
      Epub 2007 Jul 26.