Abstract
We established an anti-ErbB-2 mouse-human chimeric monoclonal antibody (MoAb), CH401, which was able to kill cancer cells overexpressing the ErbB-2 protein in vitro. The analysis of the killing mechanism indicated that MoAb CH401 might be the first anti-erbB-2 mouse-human chimeric MoAb which can induce the apoptosis of cancer cells, since morphological changes and DNA fragmentation were recognized in MoAb CH401-treated cells. The ErbB-2 receptor appears to have two opposing functions: acting as a receptor both for a growth factor and for an apoptotic factor. Our results indicate that MoAb CH401 treatment may prove to be very useful for cancer therapy.
MeSH Terms
Animals
Antibodies, Monoclonal
Apoptosis
Cell Cycle
DNA Fragmentation
Humans
Mice
Neoplasms/metabolism,pathology
Phosphorylation
Protein-Tyrosine Kinases/metabolism
Receptor, ErbB-2/immunology
Recombinant Fusion Proteins/immunology
Time Factors
Tumor Cells, Cultured
Chemicals
Antibodies, Monoclonal
Recombinant Fusion Proteins
Protein-Tyrosine Kinases
Receptor, ErbB-2
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Sasaki S
First Department of Internal Medicine, Sapporo Medical University.
Tsujisaki M
Jinnohara T
Ishida T
Sekiya M
Adachi M
Takahashi S
Hinoda Y
Imai K
References (26)
26 references, click to expand
-
p185HER2 monoclonal antibody has antiproliferative effects in vitro and sensitizes human breast tumor cells to tumor necrosis factor.
Mol Cell Biol. 1989 Mar;9(3):1165-72
PMID: 2566907
-
Amplification of c-erbB-2 oncogene in human adenocarcinomas in vivo.
Lancet. 1986 Apr 5;1(8484):765-7
PMID: 2870269
-
Monoclonal antibodies as agonists: an expanded role for their use in cancer therapy.
Cancer Res. 1994 Oct 15;54(20):5301-9
PMID: 7923157
-
Establishment and characterization of mouse-human chimeric monoclonal antibody to erbB-2 product.
Jpn J Cancer Res. 1994 Feb;85(2):172-8
PMID: 7908285
-
A human/mouse chimeric monoclonal antibody against intercellular adhesion molecule-1 for tumor radioimmunoimaging.
Jpn J Cancer Res. 1996 Apr;87(4):405-11
PMID: 8641973
-
Tumor-inhibitory monoclonal antibodies to the HER-2/Neu receptor induce differentiation of human breast cancer cells.
Cancer Res. 1992 May 1;52(9):2580-9
PMID: 1373672
-
Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer.
Science. 1989 May 12;244(4905):707-12
PMID: 2470152
-
Down-modulation of an oncogene protein product and reversion of the transformed phenotype by monoclonal antibodies.
Cell. 1985 Jul;41(3):697-706
PMID: 2860972
-
Differential responses of human tumor cell lines to anti-p185HER2 monoclonal antibodies.
Cancer Immunol Immunother. 1993 Sep;37(4):255-63
PMID: 8102322
-
Overexpression of the c-erbB-2 oncoprotein in human breast carcinomas: immunohistological assessment correlates with gene amplification.
Lancet. 1987 Jul 11;2(8550):69-72
PMID: 2885574
-
Prevention of breast tumour development in vivo by downregulation of the p185neu receptor.
Nat Med. 1995 Jul;1(7):644-8
PMID: 7585144
-
Antibody-induced growth inhibition is mediated through immunochemically and functionally distinct epitopes on the extracellular domain of the c-erbB-2 (HER-2/neu) gene product p185.
Int J Cancer. 1993 Feb 1;53(3):401-8
PMID: 7679090
-
Suppression and promotion of tumor growth by monoclonal antibodies to ErbB-2 differentially correlate with cellular uptake.
Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3353-7
PMID: 7724565
-
Significance of erbB-2 gene product as a target molecule for cancer therapy.
Scand J Immunol. 1994 May;39(5):459-66
PMID: 7910704
-
Monoclonal antibody therapy of human cancer: taking the HER2 protooncogene to the clinic.
J Clin Immunol. 1991 May;11(3):117-27
PMID: 1679763
-
Agonistic antibodies stimulate the kinase encoded by the neu protooncogene in living cells but the oncogenic mutant is constitutively active.
Proc Natl Acad Sci U S A. 1990 Apr;87(7):2569-73
PMID: 1969636
-
Apoptosis induced by an anti-epidermal growth factor receptor monoclonal antibody in a human colorectal carcinoma cell line and its delay by insulin.
J Clin Invest. 1995 Apr;95(4):1897-905
PMID: 7706497
-
Inhibition of tumor growth by a monoclonal antibody reactive with an oncogene-encoded tumor antigen.
Proc Natl Acad Sci U S A. 1986 Dec;83(23):9129-33
PMID: 3466178
-
Monoclonal antibodies specific for the neu oncogene product directly mediate anti-tumor effects in vivo.
Oncogene. 1988 Apr;2(4):387-94
PMID: 2896329
-
Characterization of murine monoclonal antibodies reactive to either the human epidermal growth factor receptor or HER2/neu gene product.
Cancer Res. 1990 Mar 1;50(5):1550-8
PMID: 1689212
-
Monoclonal antibodies directed to the erbB-2 receptor inhibit in vivo tumour cell growth.
Br J Cancer. 1993 Dec;68(6):1140-5
PMID: 7903153
-
Amplification of a novel v-erbB-related gene in a human mammary carcinoma.
Science. 1985 Sep 6;229(4717):974-6
PMID: 2992089
-
A v-erbB-related protooncogene, c-erbB-2, is distinct from the c-erbB-1/epidermal growth factor-receptor gene and is amplified in a human salivary gland adenocarcinoma.
Proc Natl Acad Sci U S A. 1985 Oct;82(19):6497-501
PMID: 2995967
-
A cell-killing monoclonal antibody (anti-Fas) to a cell surface antigen co-downregulated with the receptor of tumor necrosis factor.
J Exp Med. 1989 May 1;169(5):1747-56
PMID: 2469768
-
Selection of monoclonal antibodies which induce internalization and phosphorylation of p185HER2 and growth inhibition of cells with HER2/NEU gene amplification.
Int J Cancer. 1991 Apr 1;47(6):933-7
PMID: 1672668
-
Mechanistic aspects of the opposing effects of monoclonal antibodies to the ERBB2 receptor on tumor growth.
Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8691-5
PMID: 1717984