PMID- 10950153
OWN - NLM
STAT- MEDLINE
DCOM- 20000906
LR  - 20190831
IS  - 0344-5704 (Print)
IS  - 0344-5704 (Linking)
VI  - 46 Suppl
DP  - 2000
TI  - Development of a cancer vaccine: peptides, proteins, and DNA.
PG  - S77-82
AB  - Genetic changes leading to protooncogene activation qualitatively and/or 
      quantitatively alter their gene products and are exclusively or largely 
      restricted to transforming cells and their precursors. The overexpression of HER2 
      is among those changes and is often detected in adenocarcinomas such as breast, 
      ovarian, lung, and gastric cancer. This provides a rationale for exploring the 
      possibility that HER2 is a target of host immune responses against cancer cells. 
      We have recently demonstrated that HER2 can be a target for tumor-rejecting 
      immune responses against syngeneic murine HER2+ tumor cells. We defined two 
      different peptides, HER2p63-71 and HER2p780-788, with a Kd anchor motif that can 
      induce CD8+ cytotoxic T lymphocytes (CTLs). The growth of HER2+ syngeneic tumors 
      was suppressed in mice immunized with HER2p63-71 or p780-788. Since murine Kd and 
      human HLA-A24 share a similar anchor motif for peptides, HER2p63 71 and 
      HER2p780-788 were examined for induction of CTLs in HLA-A24+ individuals. CD8+ 
      CTL clones specific for these peptides were established and they lysed HER2+ 
      tumor cells in a human leukocyte antigen (HLA)-A24-restricted manner. To elicit 
      specific CD8+ T cell immune responses against cancer, the development of 
      efficient devices to deliver tumor antigen peptides to the major 
      histocompatibility complex (MHC) class I pathway constitutes a central issue. We 
      have developed a novel formula of hydrophobized polysaccharide nanoparticles 
      which can deliver a HER2 oncoprotein containing an epitope peptide to the MHC 
      class I pathway. We designed a simple protein delivery system: cholesteryl 
      group-bearing polysaccharides, mannan or pullulan (CHM or CHP, respectively), 
      complexed with the truncated HER2 protein containing the 147 N-terminal amino 
      acids. These complexes were able to induce CD8+ CTLs against HER2+ tumors. CTLs 
      were MHC class I restricted and specifically recognized HER2p63-71, a part of a 
      truncated HER2 protein used as an immunogen. The complete rejection of tumors 
      also occurred when CHM-HER2 was applied early after tumor implantation. In the 
      effector phase of in vivo tumor rejection, CD8+ T cells played a major role. The 
      results suggest that this unique hydrophobized polysaccharide may help soluble 
      proteins to induce cellular immunity. Such a novel vaccine may be of potential 
      benefit in cancer prevention and cancer therapy.
FAU - Shiku, H
AU  - Shiku H
AD  - Second Department of Internal Medicine, Mie University School of Medicine, Tsu, 
      Mie, Japan.
FAU - Wang, L
AU  - Wang L
FAU - Ikuta, Y
AU  - Ikuta Y
FAU - Okugawa, T
AU  - Okugawa T
FAU - Schmitt, M
AU  - Schmitt M
FAU - Gu, X
AU  - Gu X
FAU - Akiyoshi, K
AU  - Akiyoshi K
FAU - Sunamoto, J
AU  - Sunamoto J
FAU - Nakamura, H
AU  - Nakamura H
LA  - eng
PT  - Journal Article
PL  - Germany
TA  - Cancer Chemother Pharmacol
JT  - Cancer chemotherapy and pharmacology
JID - 7806519
RN  - 0 (Cancer Vaccines)
RN  - 0 (DNA, Complementary)
RN  - 0 (Glucans)
RN  - 0 (Mannans)
RN  - 8ZQ0AYU1TT (pullulan)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Animals
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - Cancer Vaccines/administration & dosage/genetics/*immunology
MH  - DNA, Complementary/*genetics
MH  - Dendritic Cells/immunology
MH  - Female
MH  - Fibrosarcoma/genetics/immunology
MH  - Glucans/administration & dosage
MH  - Humans
MH  - Lymphocyte Activation/immunology
MH  - Mannans/administration & dosage
MH  - Mast-Cell Sarcoma/genetics/immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred DBA
MH  - Receptor, ErbB-2/administration & dosage/*genetics/*immunology
MH  - T-Lymphocytes, Cytotoxic/*immunology
MH  - T-Lymphocytes, Regulatory/immunology
MH  - Transfection
MH  - Tumor Cells, Cultured
EDAT- 2000/08/19 11:00
MHDA- 2000/09/09 11:01
CRDT- 2000/08/19 11:00
PHST- 2000/08/19 11:00 [pubmed]
PHST- 2000/09/09 11:01 [medline]
PHST- 2000/08/19 11:00 [entrez]
AID - 10.1007/s002800000179 [doi]
PST - ppublish
SO  - Cancer Chemother Pharmacol. 2000;46 Suppl:S77-82. doi: 10.1007/s002800000179.