PMID- 20507323
OWN - NLM
STAT- MEDLINE
DCOM- 20100810
LR  - 20210102
IS  - 1349-7006 (Electronic)
IS  - 1347-9032 (Linking)
VI  - 101
IP  - 7
DP  - 2010 Jul
TI  - Adjuvant engineering for cancer immunotherapy: Development of a synthetic TLR2 
      ligand with increased cell adhesion.
PG  - 1596-603
LID - 10.1111/j.1349-7006.2010.01583.x [doi]
AB  - The development of effective immunoadjuvants for tumor immunotherapy is of 
      fundamental importance. The use of Mycobacterium bovis bacillus Calmette-Guerin 
      cell wall skeleton (BCG-CWS) in tumor immunotherapy has been examined in various 
      clinical applications. Because BCG-CWS is a macromolecule that cannot be 
      chemically synthesized, the development of an alternative synthetic molecule is 
      necessary to ensure a constant supply of adjuvant. In the present study, a new 
      adjuvant was designed based on the structure of macrophage-activating lipopeptide 
      (MALP)-2, which is a Toll-like receptor (TLR)-2 ligand similar to BCG-CWS. 
      Macrophage-activating lipopeptide-2, [S-(2,3-bispalmitoyloxypropyl)Cys (P2C) - 
      GNNDESNISFKEK], originally identified in a Mycoplasma species, is a lipopeptide 
      that can be chemically synthesized. A MALP-2 peptide was substituted with a 
      functional motif, RGDS, creating a novel molecule named P2C-RGDS. RGDS was 
      selected because its sequence constitutes an integrin-binding motif and various 
      integrins are expressed in immune cells including dendritic cells (DCs). Thus, 
      this motif adds functionality to the ligand. P2C-RGDS activated DCs and 
      splenocytes more efficiently than MALP-2 over short incubation times in vitro, 
      and the RGDS motif contributed to their activation. Furthermore, P2C-RGDS showed 
      higher activity than MALP-2 in inducing migration of DCs to draining lymph node, 
      and in inhibiting tumor growth in vivo. This process of designing and developing 
      synthetic adjuvants has been named "adjuvant engineering," and the evaluation and 
      improvement of P2C-RGDS constitutes a first step in the development of stronger 
      synthetic adjuvants in the future.
FAU - Akazawa, Takashi
AU  - Akazawa T
AD  - Department of Molecular Genetics, Osaka Medical Center for Cancer and 
      Cardiovascular Diseases, Osaka, Japan. akazawa-ta@mc.pref.osaka.jp
FAU - Inoue, Norimitsu
AU  - Inoue N
FAU - Shime, Hiroaki
AU  - Shime H
FAU - Kodama, Ken
AU  - Kodama K
FAU - Matsumoto, Misako
AU  - Matsumoto M
FAU - Seya, Tsukasa
AU  - Seya T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100405
PL  - England
TA  - Cancer Sci
JT  - Cancer science
JID - 101168776
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (BCG Vaccine)
RN  - 0 (Ligands)
RN  - 0 (Lipopeptides)
RN  - 0 (Oligopeptides)
RN  - 0 (Toll-Like Receptor 1)
RN  - 0 (Toll-Like Receptor 2)
RN  - AC6UDA2MFC (arginyl-glycyl-aspartyl-serine)
SB  - IM
MH  - Adjuvants, Immunologic/chemistry/therapeutic use
MH  - Amino Acid Sequence
MH  - Animals
MH  - BCG Vaccine/therapeutic use
MH  - Cell Adhesion/immunology/physiology
MH  - Cell- and Tissue-Based Therapy/methods
MH  - Dendritic Cells/immunology
MH  - Immunotherapy/*methods
MH  - Ligands
MH  - Lipopeptides/therapeutic use
MH  - Lymph Nodes/immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Neoplasms/*immunology
MH  - Oligopeptides/chemistry/immunology
MH  - Tissue Engineering/*methods
MH  - Toll-Like Receptor 1/deficiency/genetics
MH  - Toll-Like Receptor 2/*immunology
EDAT- 2010/05/29 06:00
MHDA- 2010/08/11 06:00
CRDT- 2010/05/29 06:00
PHST- 2010/05/29 06:00 [entrez]
PHST- 2010/05/29 06:00 [pubmed]
PHST- 2010/08/11 06:00 [medline]
AID - CAS1583 [pii]
AID - 10.1111/j.1349-7006.2010.01583.x [doi]
PST - ppublish
SO  - Cancer Sci. 2010 Jul;101(7):1596-603. doi: 10.1111/j.1349-7006.2010.01583.x. Epub 
      2010 Apr 5.