A new delivery system for auristatin in STxB-drug conjugate therapy

Batisse, Cornélie; Dransart, Estelle; Sarkouh, Rafik Ait; Brullé, Laura; Bai, Siau-Kun; Godefroy, Sylvie; Johannes, Ludger; Schmidt, Frédéric

doi:10.1016/j.ejmech.2015.03.047

Cited by 36 publications

(43 citation statements)

References 23 publications

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“…5). Traceless, self-immolative disulfide linkers have been used to release phosphates, 31 alcohols, 32–34 hydrazides, 35 and amines 36,37 for a variety of imaging and therapeutic applications. 11 Immolation for some of these has been proposed to occur through either cyclization to a 3-membered ring (thiirane or episulfide) or cyclization to a 5-membered cyclic thiocarbonate.…”

Section: Resultsmentioning

confidence: 99%

Decoupling stability and release in disulfide bonds with antibody-small molecule conjugates

et al. 2017

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Section: Resultsmentioning

confidence: 99%

Decoupling stability and release in disulfide bonds with antibody-small molecule conjugates

et al. 2017

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“…The conjugates were designed to enable release of the active agents under reducing conditions. in vitro studies in Gb3‐positive and Gb3‐negative HT29 colorectal cancer cells showed that the conjugates had approximately 100‐fold higher anticancer activity on Gb3‐positive cells (GI 50 in nM range) . This is in contrast to free MMAE or MMAF, whose cytotoxicities were independent of Gb3 expression.…”

Section: Targeted Delivery Of Mollusk‐derived Anticancer Agentsmentioning

confidence: 98%

“…Batisse et al . developed delivery systems that targeted MMAE and MMAF to glycosphingolipid globotriaosylceramide (Gb3, also referred to as CD77) positive cancer cells .…”

Section: Targeted Delivery Of Mollusk‐derived Anticancer Agentsmentioning

confidence: 99%

“…Batisse et al . developed delivery systems that targeted MMAE and MMAF to glycosphingolipid globotriaosylceramide (Gb3, also referred to as CD77) positive cancer cells . The systems consisted of degradable conjugates of MMAE and MMAF and the cysteine‐terminated B‐subunit of the Shiga toxin (STxB) ( 96 and 97 , respectively, Fig.…”

Section: Targeted Delivery Of Mollusk‐derived Anticancer Agentsmentioning

confidence: 99%

“…The systems consisted of degradable conjugates of MMAE and MMAF and the cysteine‐terminated B‐subunit of the Shiga toxin (STxB) ( 96 and 97 , respectively, Fig. ) . The conjugates were designed to enable release of the active agents under reducing conditions.…”

Section: Targeted Delivery Of Mollusk‐derived Anticancer Agentsmentioning

confidence: 99%

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Marine Mollusk‐Derived Agents with Antiproliferative Activity as Promising Anticancer Agents to Overcome Chemotherapy Resistance

Ciavatta

Lefranc

Carbone

et al. 2016

Medicinal Research Reviews

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The chemical investigation of marine mollusks has led to the isolation of a wide variety of bioactive metabolites, which evolved in marine organisms as favorable adaptations to survive in different environments. Most of them are derived from food sources, but they can be also biosynthesized de novo by the mollusks themselves, or produced by symbionts. Consequently, the isolated compounds cannot be strictly considered as “chemotaxonomic markers” for the different molluscan species. However, the chemical investigation of this phylum has provided many compounds of interest as potential anticancer drugs that assume particular importance in the light of the growing literature on cancer biology and chemotherapy. The current review highlights the diversity of chemical structures, mechanisms of action, and, most importantly, the potential of mollusk‐derived metabolites as anticancer agents, including those biosynthesized by mollusks and those of dietary origin. After the discussion of dolastatins and kahalalides, compounds previously studied in clinical trials, the review covers potentially promising anticancer agents, which are grouped based on their structural type and include terpenes, steroids, peptides, polyketides and nitrogen‐containing compounds. The “promise” of a mollusk‐derived natural product as an anticancer agent is evaluated on the basis of its ability to target biological characteristics of cancer cells responsible for poor treatment outcomes. These characteristics include high antiproliferative potency against cancer cells in vitro, preferential inhibition of the proliferation of cancer cells over normal ones, mechanism of action via nonapoptotic signaling pathways, circumvention of multidrug resistance phenotype, and high activity in vivo, among others. The review also includes sections on the targeted delivery of mollusk‐derived anticancer agents and solutions to their procurement in quantity.

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A real‐time cell‐binding assay reveals dynamic features of STxB–Gb3 cointernalization and STxB‐mediated cargo delivery into cancer cells

et al. 2020

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The interaction between the Shiga toxin B‐subunit (STxB) and its globotriaosylceramide receptor (Gb3) has a high potential for being exploited for targeted cancer therapy. The primary goal of this study was to evaluate the capacity of STxB to carry small molecules and proteins as cargo into cells. For this purpose, an assay was designed to provide real‐time information about the StxB–Gb3 interaction as well as the dynamics and mechanism of the internalization process. The assay revealed the ability to distinguish the process of binding to the cell surface from internalization and presented the importance of receptor and STxB clustering for internalization. The overall setup demonstrated that the binding mechanism is complex, and the concept of affinity is difficult to apply. Hence, time‐resolved methods, providing detailed information about the interaction of STxB with cells, are critical for the optimization of intracellular delivery.

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A new delivery system for auristatin in STxB-drug conjugate therapy

Cited by 36 publications

References 23 publications

Decoupling stability and release in disulfide bonds with antibody-small molecule conjugates

Decoupling stability and release in disulfide bonds with antibody-small molecule conjugates

Marine Mollusk‐Derived Agents with Antiproliferative Activity as Promising Anticancer Agents to Overcome Chemotherapy Resistance

A real‐time cell‐binding assay reveals dynamic features of STxB–Gb3 cointernalization and STxB‐mediated cargo delivery into cancer cells

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