PMID- 21705450
OWN - NLM
STAT- MEDLINE
DCOM- 20120203
LR  - 20231213
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 17
IP  - 16
DP  - 2011 Aug 15
TI  - Induction of HLA-DP4-restricted anti-survivin Th1 and Th2 responses using an 
      artificial antigen-presenting cell.
PG  - 5392-401
LID - 10.1158/1078-0432.CCR-10-3083 [doi]
AB  - PURPOSE: In previous cancer vaccine clinical trials targeting survivin, induction 
      of specific CD8(+) T-cell responses did not consistently lead to clinical 
      responses. Considering the critical role of CD4(+) T-cell help in generating 
      antitumor immunity, integration of anti-survivin CD4(+) T-cell responses may 
      enhance the efficacy of anti-survivin cancer immunotherapy. Human leukocyte 
      antigen (HLA)-DP4 is emerging as an attractive MHC target allele of CD4(+) T 
      cell-mediated immunotherapy, because it is one of the most frequent HLA alleles 
      in many ethnic groups. In this article, we aimed to elucidate DP4-restricted 
      CD4(+) T-cell responses against survivin in cancer patients. EXPERIMENTAL DESIGN: 
      We generated a human cell-based artificial antigen-presenting cell (aAPC) 
      expressing HLA-DP4, CD80, and CD83 and induced DP4-restricted antigen-specific 
      CD4(+) T cells. The number, phenotype, effector function, and in vitro longevity 
      of generated CD4(+) T cells were determined. RESULTS: We first determined 
      previously unknown DP4-restricted CD4(+) T-cell epitopes derived from 
      cytomegalovirus pp65, to which sustained Th1-biased recall responses were induced 
      in vitro by using DP4-aAPC. In contrast, DP4-aAPC induced in vitro both Th1 and 
      Th2 long-lived anti-survivin CD4(+) T cells from cancer patients. Both 
      survivin-specific Th1 and Th2 cells were able to recognize survivin-expressing 
      tumors in a DP4-restricted manner. Neither survivin-specific interleukin 10 
      secreting Tr1 cells nor Th17 cells were induced by DP4-aAPC. CONCLUSIONS: 
      DP4-restricted anti-survivin Th1 and Th2 immunity with sufficient functional 
      avidity can be induced from cancer patients. The development of strategies to 
      concurrently induce both CD4(+) and CD8(+) T-cell responses against survivin is 
      warranted for optimal anti-survivin cancer immunotherapy.
CI  - (c)2011 AACR.
FAU - Tanaka, Makito
AU  - Tanaka M
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, USA.
FAU - Butler, Marcus O
AU  - Butler MO
FAU - Ansen, Sascha
AU  - Ansen S
FAU - Imataki, Osamu
AU  - Imataki O
FAU - Berezovskaya, Alla
AU  - Berezovskaya A
FAU - Nadler, Lee M
AU  - Nadler LM
FAU - Hirano, Naoto
AU  - Hirano N
LA  - eng
GR  - K22 CA129240-02/CA/NCI NIH HHS/United States
GR  - R01CA148673/CA/NCI NIH HHS/United States
GR  - R01 CA148673-01/CA/NCI NIH HHS/United States
GR  - K22 CA129240-01/CA/NCI NIH HHS/United States
GR  - K22 CA129240-03/CA/NCI NIH HHS/United States
GR  - R01 CA148673-02/CA/NCI NIH HHS/United States
GR  - R01 CA148673/CA/NCI NIH HHS/United States
GR  - K22 CA129240/CA/NCI NIH HHS/United States
GR  - K22CA129240/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110624
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Antigens, CD)
RN  - 0 (B7-1 Antigen)
RN  - 0 (BIRC5 protein, human)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-DP beta-Chains)
RN  - 0 (HLA-DPw4 antigen)
RN  - 0 (Immunoglobulins)
RN  - 0 (Inhibitor of Apoptosis Proteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Survivin)
RN  - 0 (Viral Matrix Proteins)
RN  - 0 (cytomegalovirus matrix protein 65kDa)
RN  - 207137-56-2 (Interleukin-4)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Alleles
MH  - Amino Acid Sequence
MH  - Antigen-Presenting Cells/*immunology/metabolism
MH  - Antigens, CD/immunology/metabolism
MH  - B7-1 Antigen/immunology/metabolism
MH  - Blotting, Western
MH  - CD4-Positive T-Lymphocytes/immunology/metabolism
MH  - CD8-Positive T-Lymphocytes/immunology/metabolism
MH  - Epitopes, T-Lymphocyte/immunology/metabolism
MH  - Flow Cytometry
MH  - HLA-DP beta-Chains/genetics/*immunology/metabolism
MH  - Humans
MH  - Immunoglobulins/immunology/metabolism
MH  - Immunotherapy/methods
MH  - Inhibitor of Apoptosis Proteins/*immunology
MH  - Interferon-gamma/immunology/metabolism
MH  - Interleukin-4/immunology/metabolism
MH  - K562 Cells
MH  - Membrane Glycoproteins/immunology/metabolism
MH  - Molecular Sequence Data
MH  - Neoplasms/immunology/metabolism/therapy
MH  - Phosphoproteins/immunology
MH  - Survivin
MH  - Th1 Cells/*immunology/metabolism
MH  - Th2 Cells/*immunology/metabolism
MH  - Viral Matrix Proteins/immunology
MH  - CD83 Antigen
PMC - PMC3156899
MID - NIHMS307728
EDAT- 2011/06/28 06:00
MHDA- 2012/02/04 06:00
PMCR- 2012/08/15
CRDT- 2011/06/28 06:00
PHST- 2011/06/28 06:00 [entrez]
PHST- 2011/06/28 06:00 [pubmed]
PHST- 2012/02/04 06:00 [medline]
PHST- 2012/08/15 00:00 [pmc-release]
AID - 1078-0432.CCR-10-3083 [pii]
AID - 10.1158/1078-0432.CCR-10-3083 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2011 Aug 15;17(16):5392-401. doi: 10.1158/1078-0432.CCR-10-3083. 
      Epub 2011 Jun 24.