Tumor Vascular Targeting Using a Tumor-Tissue Endothelium-Specific Monoclonal Antibody as an Effective Strategy for Cancer Chemotherapy

Makimoto, Hiroo; Koizumi, Keiichi; Tsunoda, Shin-ichi; Wakai, Yukiko; Matsui, Junji; Tsutsumi, Yasuo; Nakagawa, Shinsaku; Ohizumi, Iwao; Taniguchi, Kenji; Saito, Hiroyuki; Utoguchi, Naoki; Ohsugi, Yoshiyuki; Mayumi, Tadanori

doi:10.1006/bbrc.1999.0647

Cited by 9 publications

(4 citation statements)

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“…Many other researchers have prepared [130,131,132,133] and used antibody-drug conjugates [134,135,136], liposome conjugates [137,138,139], polymer-drug [140,141,142, Fig. (45).…”

Section: -Hydrazone Linkagesmentioning

confidence: 99%

Reversible Covalent Chemistry in Drug Delivery

West

Otto

2005

CDDT

150

109

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The targeting of drugs specifically to their sites of action is an important strategy for increasing drug efficacy. Chemists have come up with many elegant schemes that aim to convert drugs into magic bullets. This review focuses on the chemistry that underlies these schemes, with particular emphasis on two types of cleavable covalent bonds that are frequently used to link drugs to their various carriers: disulfide bonds and hydrazone bonds. These linkages have been used to release drugs under specific conditions; in the case of disulfides, cleavage is triggered by the mildly reducing environment found in intracellular fluids, and in the case of hydrazones, the acidic conditions that prevail in endosomes cause release of the drug. The applications of these chemistries in drug delivery are reviewed.

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“…Many other researchers have prepared [130,131,132,133] and used antibody-drug conjugates [134,135,136], liposome conjugates [137,138,139], polymer-drug [140,141,142, Fig. (45).…”

Section: -Hydrazone Linkagesmentioning

confidence: 99%

Reversible Covalent Chemistry in Drug Delivery

West

Otto

2005

CDDT

150

109

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“…Monoclonal antibodies designed to target tumour endothelial cell‐specific epitopes have also been tested in animal studies. Antibodies that bind specifically to tumour endothelial cells have been identified from the isolation of these cells from solid tumours (Makimoto et al . 1999).…”

Section: Current Approaches To Tumour Vascular Targetingmentioning

confidence: 99%

The biology of the combretastatins as tumour vascular targeting agents

Tozer

Kanthou

Parkins

et al. 2002

Int J Experimental Path

303

186

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Summary The tumour vasculature is an attractive target for therapy. Combretastatin A‐4 (CA‐4) and A‐1 (CA‐1) are tubulin binding agents, structurally related to colchicine, which induce vascular‐mediated tumour necrosis in animal models. CA‐1 and CA‐4 were isolated from the African bush willow, Combretum caffrum, and several synthetic analogues are also now available, such as the Aventis Pharma compound, AVE8062. More soluble, phosphated, forms of CA‐4 (CA‐4‐P) and CA‐1 (CA‐1‐P) are commonly used for in vitro and in vivo studies. These are cleaved to the natural forms by endogenous phosphatases and are taken up into cells. The lead compound, CA‐4‐P, is currently in clinical trial as a tumour vascular targeting agent. In animal models, CA‐4‐P causes a prolonged and extensive shut‐down of blood flow in established tumour blood vessels, with much less effect in normal tissues. This paper reviews the current understanding of the mechanism of action of the combretastatins and their therapeutic potential.

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“…The degree of substitution with PDPH was determined as previously reported. 16) The conjugation rate was calculated to be approximately 4.5 mol of PDPH per mol of antibody. NCS, kindly provided by Dr. M. Hirama (Tohoku University, Sendai), was incubated with a tenfold molar excess of 2-iminothiolane (IT; Pierce) in 0.1 M phosphate buffer, pH 8.0, for 45 min at 25°C in the dark.…”

Section: Methodsmentioning

confidence: 99%

“…15) Next, we immunoconjugated TES-23 with neocarzinostatin (NCS). 16) In the present report, we describe the anti-tumor effects of the immunoconjugate in the treatment of mice bearing Meth-A fibrosarcoma as part of a program to examine the applicability of this approach to different types of tumors. Mice treated with the immunoconjugate showed improved survival with no side effects.…”

mentioning

confidence: 99%