Novel doxorubicin-monoclonal anti-carcinoembryonic antigen antibody immunoconjugate activity in vitro

Lau, Achilles; Bérubé, Gervais; Ford, C. H. J.; Gallant, Maureen

doi:10.1016/0968-0896(95)00126-2

Cited by 30 publications

(27 citation statements)

References 17 publications

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“…Dessicated anti-HER2/ neu monoclonal immunoglobulin (1.5 mg) was combined with 2-iminothiolane (2-IT: 6.5 mM final concentration) in PBS (0.1 M, pH 8.0, 250 μl) and incubated at 25°C for 1.5 hours in combination with simultaneous constant gentle stirring [11,38-40]. Thiolated anti-HER2/ neu monoclonal immunoglobulin was then buffer exchanged into PBS-EDTA (phosphate 0.1, NaCl 0.15 M, EDTA 10 mM, pH 7.3) using micro-scale column chromatography.…”

Section: Methodsmentioning

confidence: 99%

Epirubicin-[Anti-HER2/neu] Synthesized with an Epirubicin-(C13-imino)-EMCS Analog: Anti-Neoplastic Activity against Chemotherapeutic-Resistant SKBr-3 Mammary Carcinoma in Combination with Organic Selenium

Coyne¹,

Jones²,

Syguła³

et al. 2011

JCT

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Purpose Discover the anti-neoplastic efficacy of epirubicin-(C13-imino)-[anti-HER2/neu] against chemotherapeutic-resistant SKBr-3 mammary carcinoma and delineate the capacity of selenium to enhance it’s cytotoxic anti-neoplastic potency. Methods In molar excess, EMCH was combined with epirubicin to create a covalent epirubicin-(C13-imino)-EMCH-maleimide intermediate with sulfhydryl-reactive properties. Monoclonal immunoglobulin selective for HER2/neu was then thiolated with 2-iminothiolane at the terminal ε-amine group of lysine residues. The sulfhydryl-reactive epirubicin-(C13-imino)-EMCH intermediate was then combined with thiolated anti-HER2/neu monoclonal immunoglobulin. Western-blot analysis was utilized to characterize the molecular weight profiles while binding of epirubicin-(C13-imino)-[anti-HER2/neu] to membrane receptors was determined by cell-ELISA utilizing populations of SKBr-3 mammary carcinoma that highly over-expresses HER2/neu complexes. Anti-neoplastic potency of epirubicin-(C13-imino)-[anti-HER2/neu] between the epirubicin-equivalent concentrations of 10−12 M and 10−7 M was determined by vitality staining analysis with and without the presence of selenium (5 μM). Results Epiribucin-(C13-imino)-[anti-HER2/neu] between epirubicin-equivalent concentrations of 10−8 M to 10−7 M consistently evoked higher anti-neoplastic potency than “free” non-conjugated epirubicin which corresponded with previous investigations utilizing epirubicin-(C3-amide)-[anti-HER2/neu] and epirubicin-(C3-amide)-[anti-EGFR]. Selenium at 5 mM consistently enhanced the cytotoxic anti-neoplastic potency of epirubicin-(C13-imino)-[anti-HER2/neu] at epirubicin equivalent concentrations (10–12 to 10–7 M). Conclusions Epirubicin-(C13-imino)-[anti-HER2/neu] is more potent than epirubicin against chemotherapeutic-resistant SKBr-3 mammary carcinoma and selenium enhances epirubicin-(C13-imino)-[anti-HER2/neu] potency. The methodology applied for synthesizing epirubicin-(C13-imino)-[anti-HER2/neu] is relatively time convenient and has low instrumentation requirements.

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Section: Methodsmentioning

confidence: 99%

Epirubicin-[Anti-HER2/neu] Synthesized with an Epirubicin-(C13-imino)-EMCS Analog: Anti-Neoplastic Activity against Chemotherapeutic-Resistant SKBr-3 Mammary Carcinoma in Combination with Organic Selenium

Coyne¹,

Jones²,

Syguła³

et al. 2011

JCT

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“…30,71,73,92,93 Similar molecular strategies have been employed to synthesize covalent anthracycline immunochemotherapeutics through the formation of a covalent bond with the a-monoamine (C 3 -amine) group on the carbohydrate moiety of doxorubicin, daunorubicin, or epirubicin. 10,15,17,[20][21][22][23][24][25]27,28,32,19 Generation of a covalent bond at the C 5 -methylhydroxy group of gemcitabine represents a second alternative molecular strategy for synthesizing covalent gemcitabineligand conjugates. 61,[68][69][70][71][72][73] Gemcitabine has been covalently bound to a number of biologically relevant ligands.…”

Section: Generalmentioning

confidence: 99%

Synthesis of a covalent gemcitabine-(carbamate)-[anti-HER2/neu] immunochemotherapeutic and its cytotoxic anti-neoplastic activity against chemotherapeutic-resistant SKBr-3 mammary carcinoma

Coyne

Jones

Pharr

2011

Bioorganic & Medicinal Chemistry

137

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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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Novel doxorubicin-monoclonal anti-carcinoembryonic antigen antibody immunoconjugate activity in vitro

Cited by 30 publications

References 17 publications

Epirubicin-[Anti-HER2/neu] Synthesized with an Epirubicin-(C13-imino)-EMCS Analog: Anti-Neoplastic Activity against Chemotherapeutic-Resistant SKBr-3 Mammary Carcinoma in Combination with Organic Selenium

Epirubicin-[Anti-HER2/neu] Synthesized with an Epirubicin-(C13-imino)-EMCS Analog: Anti-Neoplastic Activity against Chemotherapeutic-Resistant SKBr-3 Mammary Carcinoma in Combination with Organic Selenium

Synthesis of a covalent gemcitabine-(carbamate)-[anti-HER2/neu] immunochemotherapeutic and its cytotoxic anti-neoplastic activity against chemotherapeutic-resistant SKBr-3 mammary carcinoma

Reversible Covalent Chemistry in Drug Delivery

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