Antibody-Based Therapy Targeting Tumor Vascular Endothelial Cells Suppresses Solid Tumor Growth in Rats

Ohizumi, Iwao; Tsunoda, Shin-ichi; Taniguchi, Kenji; Saito, Hiroyuki; Esaki, Keiko; Makimoto, Hiroo; Wakai, Yukiko; Tsutsumi, Yasuo; Nakagawa, Shinsaku; Utoguchi, Naoki; Kaiho, Shin-ichi; Ohsugi, Yoshiyuki; Mayumi, Tadanori

doi:10.1006/bbrc.1997.6989

Cited by 13 publications

(6 citation statements)

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“…No obvious anti-tumour effects were seen with MOPC-NCS, a negative control. In addition, unconjugated TES-23, in a dose of 107 µg kg -1 , did not show an antitumour effect, but a higher dose (10 mg kg -1 ) caused growth inhibition of tumours (Ohizumi et al, 1997). …”

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confidence: 84%

“…bjoc.1999 Received 30 June 1998 Revised 2 December 1998 Accepted 12 May 1999 Correspondence to: T Mayumi antibody (TES-23) that recognizes TECs by means of actively immunizing mice with membranes of TECs after passive immunization with endothelial cells derived from normal tissue (Ohizumi et al, 1997). This study was conducted to assess the distribution of the antigen recognized by TES-23 in many tumour types in mice, rats and humans, and suggests the usefulness of TES-23 for a targeting therapy against tumour vasculature.…”

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confidence: 99%

“…TECs will make it possible to discover new antigens specific to tumour vascular endothelium. We produced a monoclonal Specific binding of TES-23 antibody to tumour vascular endothelium in mice, rats and human cancer tissue: a novel drug carrier for cancer targeting therapy antibody (TES-23) that recognizes TECs by means of actively immunizing mice with membranes of TECs after passive immunization with endothelial cells derived from normal tissue (Ohizumi et al, 1997). This study was conducted to assess the distribution of the antigen recognized by TES-23 in many tumour types in mice, rats and humans, and suggests the usefulness of TES-23 for a targeting therapy against tumour vasculature.…”

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Specific binding of TES-23 antibody to tumour vascular endothelium in mice, rats and human cancer tissue: A novel drug carrier for cancer targeting therapy

et al. 1999

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SummaryThe tissue distribution of anti-tumour vascular endothelium monoclonal antibody (TES-23) produced by immunizing with plasma membrane vesicles from isolated rat tumour-derived endothelial cells (TECs) was assessed in various tumour-bearing animals. Radiolabelled TES-23 dramatically accumulated in KMT-17 fibrosarcoma, the source of isolated TECs after intravenous injection. In Meth-A fibrosarcoma, Colon-26 adenocarcinoma in BALB/c mice and HT-1080 human tumour tissue in nude mice, radioactivities of 125 I-labelled TES-23 were also up to 50 times higher than those of control antibody with little distribution to normal tissues. The selective recognition of TES-23 to TECs was competitively blocked by preadministration of unlabelled TES-23 in vivo. Furthermore, immunostaining of human tissue sections showed specific binding of TES-23 on endothelium in oesophagus cancers. These results indicate that tumour vascular endothelial cells express common antigen in different tumour types of various animal species. In order to clarify the efficacy of TES-23 as a drug carrier, an immunoconjugate, composed of TES-23 and neocarzinostatin, was tested for its anti-tumour effect in rats bearing KMT-17 fibrosarcomas. The immunoconjugate (TES-23-NCS) caused marked regression of the tumour, accompanied by haemorrhagic necrosis. Thus, from a clinical view, TES-23 would be a novel drug carrier because of its high specificity to tumour vascular endothelium and its application to many types of cancer. © 1999 Cancer Research Campaign Keywords: tumour vascular endothelium; immunoconjugate; targeting therapy; drug delivery system; monoclonal antibody 1155British Journal of Cancer (1999) 81(7), 1155-1161 © 1999 Cancer Research Campaign Article no. bjoc.1999 Received 30 June 1998 Revised 2 December 1998 Accepted 12 May 1999 Correspondence to: T Mayumi antibody (TES-23) that recognizes TECs by means of actively immunizing mice with membranes of TECs after passive immunization with endothelial cells derived from normal tissue (Ohizumi et al, 1997). This study was conducted to assess the distribution of the antigen recognized by TES-23 in many tumour types in mice, rats and humans, and suggests the usefulness of TES-23 for a targeting therapy against tumour vasculature. MATERIALS AND METHODS Isolation of tumour endothelial cellsTECs, or capillary endothelial cells in tumour tissue, were isolated from KMT-17 rat fibrosarcoma (kindly donated by Dr N Takeichi, Hokkaido University, Japan) by means of density-gradient centrifugation and attach-speed separation techniques as we previously reported (Utoguchi et al, 1995a). Briefly, minced and collagenasedigested KMT-17 tumour tissue was separated by Percoll (Amersham Pharmacia Biotech, Sweden) density-gradient centrifugation. The cells in the fraction enriched with endothelial cells were plated on tissue culture dishes in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal calf serum (FCS) and 50 µg ml -1 of endothelial cell growth supplement (ECGS, Sigma Chemical Co., St Lo...

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Specific binding of TES-23 antibody to tumour vascular endothelium in mice, rats and human cancer tissue: A novel drug carrier for cancer targeting therapy

et al. 1999

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“…In one study where anti-VEGF antibodies were delivered into nude mice tumour va.sculature, the vessels were inhibited and growth of human tumour xenografts was inhibited completely (Burrows and Thorpe, 1993). Another animal study demonstrated similar reductions in tumour growth (Ohizumi et al, 1997). VECs supplying the tumour could be targeted with a therapeutic gene by putting a VEGFR promoter in front of the gene and delivering it thus.…”

Section: Targeting To Tumour Vecsmentioning

confidence: 99%

Tumour Angiogenesis, Vascular Biology and Enhanced Drug Delivery

Dass

2004

Journal of Drug Targeting

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It is now common knowledge that for a solid tumour to become life-threatening clinically, an adequate blood supply to the neoplasm has to be established. Although neovascularisation via angiogenesis leads to a subsequent rapid growth of the tumour mass, it provides the most reliable route by which neoplastic cells may be reached by cytotoxics. In addition, for a majority of tumours, the lesion's vasculature is more permeable and tortuous than that of the surrounding healthy host tissue. Such deviation potentiates selective delivery of drugs to be achieved. This review examines, from various viewpoints, the area of tumour angiogenesis and vascularisation, currently one of the most fertile and active fields of cancer research.

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“…The specific activity of radiolabeled MAbs was approximately 1 ϫ 10 10 cpm/mg. Immunoreactivity of radioiodinated MAbs was assessed by enzyme-linked immunosorbent assay (Ohizumi et al, 1997) using the non-labeled MAb as a control.…”

Section: Radiolabeling Of Mabsmentioning

confidence: 99%

Suppression of solid tumor growth by a monoclonal antibody against tumor vasculature in rats: Involvement of intravascular thrombosis and fibrinogenesis

Ohizumi¹,

Taniguchi²,

Saito³

et al. 1999

Int. J. Cancer

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We have reported that immunization of rat tumor‐derived endothelial cells (TEC) isolated from KMT‐17 solid tumors results in the generation of several monoclonal antibodies (MAbs). TES‐23, one of these MAbs, recognizes a naturally occurring 80‐kDa antigen expressed on endothelial cells of tumor blood vessels. To determine whether such MAbs can suppress solid tumor growth in vivo by impairment of endothelial cells in tumors following direct binding, we tested the biodistribution of 125I‐labeled TES‐23 in rats bearing KMT‐17 solid tumors. We also examined the effect of treatment using unconjugated TES‐23 on tumor growth and histo‐pathological changes in tumor tissues. Biodistribution studies showed localization of TES‐23 into tumor tissues 60 min after intravenous injection. TES‐23 suppressed significantly the growth of KMT‐17 solid tumors following administration for 5 days. Histo‐pathological examination showed that TES‐23 caused degeneration, apoptosis and/or necrosis and denudation of endothelial cells in viable tumor areas following local aggregation and adhesion of lymphocytes, with subsequent intravascular thrombus formation by platelets and fibrin. Our results indicate that TES‐23, which recognizes TEC, can target endothelial cells of solid tumor vasculature directly, resulting in growth suppression in vivo by reduction of blood flow due to intravascular thrombosis. Our results also suggest that targeting tumor vasculature is a potentially attractive approach for the treatment of solid tumors. Int. J. Cancer 82:853–859, 1999. © 1999 Wiley‐Liss, Inc.

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Antibody-Based Therapy Targeting Tumor Vascular Endothelial Cells Suppresses Solid Tumor Growth in Rats

Cited by 13 publications

References 13 publications

Specific binding of TES-23 antibody to tumour vascular endothelium in mice, rats and human cancer tissue: A novel drug carrier for cancer targeting therapy

Specific binding of TES-23 antibody to tumour vascular endothelium in mice, rats and human cancer tissue: A novel drug carrier for cancer targeting therapy

Tumour Angiogenesis, Vascular Biology and Enhanced Drug Delivery

Suppression of solid tumor growth by a monoclonal antibody against tumor vasculature in rats: Involvement of intravascular thrombosis and fibrinogenesis

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