PMID- 17579068
OWN - NLM
STAT- MEDLINE
DCOM- 20070807
LR  - 20201219
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 179
IP  - 1
DP  - 2007 Jul 1
TI  - Peptide vaccines of the HER-2/neu dimerization loop are effective in inhibiting 
      mammary tumor growth in vivo.
PG  - 472-82
AB  - Human epidermal growth factor receptor-2 (HER-2)/neu (ErbB2), a member of the 
      epidermal growth factor family of receptors, is overexpressed in 20-30% of breast 
      cancers. It is an attractive target for receptor-directed antitumor therapy using 
      mAbs. Unlike other epidermal growth factor receptor family members, HER-2/neu 
      does not bind a high-affinity ligand, but rather functions as the preferred 
      dimerization partner. Pertuzumab (Omnitarg) is a humanized mAb directed against 
      the HER-2/neu dimerization domain that inhibits receptor signaling. The recent 
      definition of the crystal structure of the HER-2/neu-pertuzumab complex 
      demonstrated that the receptor dimerization region encompassed residues 266-333. 
      Based on the three-dimensional structure of the complex, we have designed three 
      conformational peptide constructs (sequences 266-296, 298-333, and 315-333) to 
      mimic regions of the dimerization loop of the receptor and to characterize their 
      in vitro and in vivo antitumor efficacy. All the constructs elicited 
      high-affinity peptide Abs that inhibited multiple signaling pathways including 
      HER-2/neu-specific inhibition of cellular proliferation and cytoplasmic receptor 
      domain phosphorylation. All the peptide Abs showed Ab-dependent cellular 
      cytotoxicity to varying degrees with the 266-296 constructs being equally 
      effective as compared with Herceptin. The 266-296 peptide vaccine had 
      statistically reduced tumor onset in both transplantable tumor models (FVB/n and 
      BALB/c) and significant reduction in tumor development in two transgenic mouse 
      tumor models (BALB-neuT and VEGF(+/-)Neu2-5(+/-)). The 266-296 construct 
      represents the most promising candidate for antitumor vaccination and could also 
      be used to treat a variety of cancers with either normal or elevated expression 
      of HER-2 including breast, lung, ovarian, and prostate.
FAU - Allen, Stephanie D
AU  - Allen SD
AD  - Ohio State Biochemistry Program, and Department of Obstetrics and Gynecology, The 
      Ohio State University, Columbus, OH 43210, USA.
FAU - Garrett, Joan T
AU  - Garrett JT
FAU - Rawale, Sharad V
AU  - Rawale SV
FAU - Jones, Audra L
AU  - Jones AL
FAU - Phillips, Gary
AU  - Phillips G
FAU - Forni, Guido
AU  - Forni G
FAU - Morris, John C
AU  - Morris JC
FAU - Oshima, Robert G
AU  - Oshima RG
FAU - Kaumaya, Pravin T P
AU  - Kaumaya PT
LA  - eng
GR  - CA 84356/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - England
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Growth Inhibitors)
RN  - 0 (Peptide Fragments)
RN  - 0 (Vaccines, Subunit)
RN  - 0 (Viral Fusion Proteins)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Antineoplastic Agents/administration & dosage/chemical 
      synthesis/*immunology/metabolism
MH  - Breast Neoplasms/immunology/pathology/prevention & control
MH  - Cancer Vaccines/administration & dosage/chemical synthesis/*immunology/metabolism
MH  - Cell Line, Tumor
MH  - Cross Reactions/genetics
MH  - Dimerization
MH  - Female
MH  - Growth Inhibitors/administration & dosage/chemical 
      synthesis/*immunology/metabolism
MH  - Humans
MH  - Male
MH  - Mammary Neoplasms, Experimental/immunology/*pathology/*prevention & control
MH  - Measles virus/genetics/immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Transgenic
MH  - Molecular Sequence Data
MH  - Peptide Fragments/administration & dosage/chemical 
      synthesis/*immunology/metabolism
MH  - Protein Structure, Secondary
MH  - Rabbits
MH  - Rats
MH  - Receptor, ErbB-2/administration & dosage/chemistry/*immunology/metabolism
MH  - Vaccines, Subunit/administration & dosage/chemical 
      synthesis/*immunology/metabolism
MH  - Viral Fusion Proteins/administration & dosage/genetics/immunology
EDAT- 2007/06/21 09:00
MHDA- 2007/08/08 09:00
CRDT- 2007/06/21 09:00
PHST- 2007/06/21 09:00 [pubmed]
PHST- 2007/08/08 09:00 [medline]
PHST- 2007/06/21 09:00 [entrez]
AID - 179/1/472 [pii]
AID - 10.4049/jimmunol.179.1.472 [doi]
PST - ppublish
SO  - J Immunol. 2007 Jul 1;179(1):472-82. doi: 10.4049/jimmunol.179.1.472.