Establishment and Characterization of Mouse‐Human Chimeric Monoclonal Antibody to <i>erbB</i>‐2 Product

Ishida, Tadao; Tsujisaki, Masayuki; Hinoda, Yuji; Imai, Kohzoh; Yachi, Akira

doi:10.1111/j.1349-7006.1994.tb02079.x

Cited by 23 publications

(29 citation statements)

References 24 publications

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“…Based upon these concepts, many therapeutic approaches have been developed which target the erbB-2 oncoprotein (31 ). For example, specific antibody-based approaches have been explored using antitumor erbB-2 antibodies or anti-erbB-2 antibodies conjugated to specific antitumor moieties (32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42).…”

Section: Discussionmentioning

confidence: 99%

Targeted tumor killing via an intracellular antibody against erbB-2.

Deshane¹,

Siegal²,

Alvarez³

et al. 1995

J. Clin. Invest.

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Specific killing of erbB-2-overexpressing tumor cells can be achieved using expression of an intracellular antibody directed against the erbB-2 oncoprotein. We have developed a strategy using a recombinant adenovirus encoding an anti-erbB-2 single chain antibody to achieve targeted tumor cell killing in vivo and can show significantly prolonged survival of animals carrying a human ovarian carcinoma tumor burden within their peritoneal cavities. This strategy of gene therapy for ovarian carcinoma offers the potential to achieve highly specific, targeted killing of human tumor cells and thus establishes the rationale to undertake human clinical trials on this basis. (J. Clin. Invest. 1995. 96:2980-2989

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Section: Discussionmentioning

confidence: 99%

Targeted tumor killing via an intracellular antibody against erbB-2.

Deshane¹,

Siegal²,

Alvarez³

et al. 1995

J. Clin. Invest.

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“…29) Indeed, CH401 was much more efficient than the mouse mAb E401 in antibody-dependent cell-mediated cytotoxicity assay (ADCC) with human effector cells. 29) The most striking finding was its in vivo anti-tumor effect. The efficacy of CH401 therapy was tested on the growth of gastric cancer JRST cells using a mouse model with tumor xenografts.…”

Section: Anti-her2 Mabsmentioning

confidence: 99%

Monoclonal antibodies as effective therapeutic agents for solid tumors

et al. 2004

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he development of a laboratory technique for making monoclonal antibodies (mAbs) by Milstein and Köhler in 1975 1) allowed the massive production of mAbs against cancer cells. Consequently, it was expected that highly specific and effective antibody therapy would be developed. However, the results obtained from several clinical trials in the early 1980s revealed limited clinical responses and adverse effects mainly due to the xenogenicity of the mAbs. Through numerous subsequent preclinical studies on a variety of mAbs, the efficacy of shutting off receptor-mediated signaling as a means of blocking cell growth and viability was noted. Remarkable objective responses were observed during clinical trials using rituximab (chimeric anti-CD20 mAb)2) or trastuzumab (humanized anti-HER2/neu/ErbB-2 mAb), 3) resulting in a second wave of mAb therapy. Various mAbs against human epidermal growth factor receptor 2 (HER2), [3][4][5][6][7] epidermal growth factor receptor (EGFR), [8][9][10][11][12][13] vascular endothelial growth factor (VEGF), 14,15) and VEGF receptor (VEGFR) 16) were then subjected to clinical trials. In addition to this mAb group, anti-idiotype mAbs are worthy of note, since they are uniquely used for active immunotherapy. This article reviews some of the recent remarkable findings concerning cancer therapy with these mAbs, especially against solid tumors. Anti-HER2 mAbsTrastuzumab (Herceptin) is a humanized mAb, which was approved by the United States Food and Drug Administration in 1998 for the treatment of advanced breast cancer. This was the first approval of a mAb for use in solid tumor therapy. Three years later, it was approved in Japan. The approved use of trastuzumab in HER2-positive metastatic diseases includes as a first-line treatment in combination with paclitaxel and as a monotherapy in patients who have received one or more chemotherapeutic regimens. HER2 overexpression is observed in 15-30% of breast cancers. 17,18) There are currently four major phase III multicenter trials that in total will randomize approximately 12,000 patients to chemotherapeutic regimens with or without trastszumab.19) HER2 expression is examined using validated fluorescence in situ hybridization or immunohistochemistry assays. The duration of trastuzumab maintenance is 1 or 2 years after chemotherapy with or without trastuzumab. In Japan, Sawaki et al. 20) reported the clinical response of 27 metastatic breast cancer patients to trastuzumab as a single agent. Complete response, partial response, no change, and progressive disease were observed in 3, 3, 3 and 17 patients, respectively, with one case being not evaluated, and the therapy was well tolerated.The most serious, but unexpected, toxicity observed during the pivotal trials was cardiac dysfunctions, including clinically manageable left ventricular systolic dysfunction, and occasionally advanced congestive heart failure in a small percentage of patients.21) The incidence and severity of cardiac dysfunction was greatest in patients receiving concomitant tras...

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“…The anti-ErbB-2 mouse MoAbs E907 and E401, and the mouse-human chimeric MoAb CH401, each of which recognizes an epitope existing within amino acids 292-370 of the extracellular domain of the human ErbB-2 receptor, 9,10) were used. These antibodies were of the IgG1 subclass.…”

Section: Moabsmentioning

confidence: 99%

“…9,10) The mouse-human chimeric anti-intercellular adhesion molecule-1 (ICAM-1) MoAb chHA58 of class IgG1 was used as a control.…”

Section: Moabsmentioning

confidence: 99%

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Human Tumor Growth Suppression by Apoptosis Induced with Anti‐ErbB‐2 Chimeric Monoclonal Antibody

Sasaki¹,

Tsujisaki²,

Jinnohara³

et al. 1998

Japanese Journal of Cancer Research

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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. Key words:ErbB-2 -Apoptosis -G 1 arrest -Chimeric monoclonal antibody -Growth factor receptorThe human erbB-2 gene product, which encodes a growth factor receptor with intrinsic tyrosine kinase activity, is expressed in a variety of adenocarcinomas.1-5) Many anti-ErbB-2 monoclonal antibodies (MoAbs) have been developed.6-8) ErbB-2 protein has the following advantages as a target molecule: [1] it is a receptor-type molecule expressed on the cancer cell surface; [2] the expression level in normal adult human tissues is very low; [3] the shedding level of this antigen as well as the incidence of positivity for circulating ErbB-2 antigen in gastrointestinal malignant diseases is very low. Accordingly, the blocking effect of circulating antigen on the function of anti-ErbB-2 MoAb should be negligible. 9)Overexpression on cancer cells and extracellular accessibility of the ErbB-2 protein enable it to be a potential target, so anti-ErbB-2 MoAbs seem promising for immunotherapy.Four anti-ErbB-2 mouse MoAbs have been established in our laboratory and characterized.9) The epitopes recognized by these MoAbs are in an extracellular domain within amino acids 292-370 of the human c-erbB-2 molecule. In vitro anti-tumor activity by these MoAbs has been measured and one of them has been selected and chimerized. A mouse-human chimeric MoAb, CH401, for ErbB-2 protein was established by a procedure using a heavy chain loss mouse mutant hybridoma and a human immunoglobulin expression vector, as described elsewhere. 9, 10)Here we show that the anti-tumor activity of this MoAb is due to the induction of apoptosis of cancer cells. MATERIALS AND METHODS MoAbsThe anti-ErbB-2 mouse MoAbs E907 and E401, and the mouse-human chimeric MoAb CH401, each of which recognizes an epitope existing within amino acids 292-370 of the extracellular domain of the human ErbB-2 receptor, 9, 10) were used. These antibodies were of the IgG1 subclass. We developed a mouse-human chimeric form (CH401) of mouse MoAb E401.10) The affinities of mouse MoAb E401 and chimeric MoAb CH401 were similar. The specificity of mouse MoAb E401 and that of chimeric MoAb CH401 have also been confirmed to be the same.10) The epitopes recognized by mouse MoAbs E907 and E401 are different.9, 10) The mouse-human chimeric anti-intercellular adhesion molecule-1 (ICAM-1) MoAb chHA58 of class IgG1 was used as a control.

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Establishment and Characterization of Mouse‐Human Chimeric Monoclonal Antibody to erbB‐2 Product

Cited by 23 publications

References 24 publications

Targeted tumor killing via an intracellular antibody against erbB-2.

Targeted tumor killing via an intracellular antibody against erbB-2.

Monoclonal antibodies as effective therapeutic agents for solid tumors

Human Tumor Growth Suppression by Apoptosis Induced with Anti‐ErbB‐2 Chimeric Monoclonal Antibody

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