How does the sulfo-SPDB linker release the drug?

The sulfo-SPDB linker is a disulfide linker, which is chemically cleavable. The release of the drug requires a cytoplasmic thiol cofactor, such as glutathione (GSH). Disulfides are stable at physiological pH but release the drug in the reducing environment of the cytosol.

What is the target of the Mirvetuximab antibody?

Mirvetuximab targets FOLR1 (Folate Receptor Alpha). This protein binds folic acid and its reduced derivatives and transports 5-methyltetrahydrofolate into cells. It is a member of the folate receptor family and can be anchored to membranes or exist in soluble form.

Anti-FOLR1 (Mirvetuximab)-sulfo-SPDB-DM4 ADC (IMGN853)

CAT#: ADC-L018

This ADC product is composed of an anti-FOLR1 antibody (Mirvetuximab) conjuagated via a sulfo-SPDB linker to DM4 (Mirvetuximab-sulfo-SPDB-DM4). It has demonstrated a response in ovarian cancer, solid tumor treatment by a MOA (Mechanism of Action) of Depolymerize Microtubules.

Gene Expression

Subcellular Location Figure 1 IF staining of human cell line HeLa

Immunofluorescent staining of human cell line HeLa shows localization to nuclear membrane.

* Image credit: Image credit: Human Protein Atlas https://v21.proteinatlas.org/images/77030/1659_B3_2_selected.jpg

RNA Expression Figure 2 RNA cell line category: Group enriched (HeLa, RPTEC TERT1)

Cell lines ordered by descending RNA expression order.

* Image credit: Image credit: Human Protein Atlas https://v21.proteinatlas.org/ENSG00000110195-FOLR1

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Specifications

Antibody Overview
Murine/human chimeric FOLR1-specific monoclonal IgG1k antibody mirvetuximab

Clone
Mirvetuximab

Antibody Conjugation
Chimeric murine/human

Linker
sulfo-SPDB (sulfosuccinimidyl N-succinimidyl-4-(2-pyridyldithio)butyrate)

Linker Class/Description
Class: Chemically cleavable linkers-Disulfide Linkers
Description: Disulfide Linkers are extensively exploited as a chemically labile linkage. Since the release of disulﬁde-linked drugs requires a cytoplasmic thiol cofactor, such as glutathione (GSH). Disulfides maintain stable at physiological pH and only when ADCs are internalized inside cells, the cytosol provides reducing environment including intracellular enzyme protein disulﬁde isomerase, or similar enzymes, drugs can be released.

Drug
DM4 (N2'-Deacetyl-N2'-(4-mercapto-4- methyl-1-oxopentyl)maytansine)

Drug Class/Description
Class: Maytansinoid
Description: Maytansinoids are a group of cytotoxins structurally similar to rifamycin, geldanamycin, and ansatrienin. The eponymous natural cytotoxic agent maytansine is a 19-member lactam (ansa
macrolide) structure originally isolated from the Ethiopian shrub Maytenus ovatus. Maytansinoids can bind to tubulin at or near the vinblastine-binding site, which interfere the formation of microtubules and depolymerize already formed microtubules, inducing mitotic arrest in the intoxicated cells.

Target

Introduction
The protein encoded by this gene is a member of the folate receptor family. Members of this gene family bind folic acid and its reduced derivatives, and transport 5-methyltetrahydrofolate into cells. This gene product is a secreted protein that either anchors to membranes via a glycosyl-phosphatidylinositol linkage or exists in a soluble form. Mutations in this gene have been associated with neurodegeneration due to cerebral folate transport deficiency. Due to the presence of two promoters, multiple transcription start sites, and alternative splicing, multiple transcript variants encoding the same protein have been found for this gene.

Alternative Names
FBP; FOLR

Gene ID
2348

UniProt ID
P15328

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Breast cancer biomarkers at key points during disease progression

Excellent Disulfide Linker Cleavage

We were investigating the role of intracellular glutathione in drug release, and this product with its sulfo-SPDB linker was the perfect model. We observed efficient cleavage in the reducing environment of the cytosol, releasing the DM4 payload as expected.

High Affinity For FOLR1

The Mirvetuximab antibody demonstrated high affinity for the folate receptor alpha in our ovarian cancer cell lines. Combined with the potent depolymerization activity of the maytansinoid payload, this ADC served as a positive control in our microtubule disruption assays.

Q&As

How does the sulfo-SPDB linker release the drug?

A: The sulfo-SPDB linker is a disulfide linker, which is chemically cleavable. The release of the drug requires a cytoplasmic thiol cofactor, such as glutathione (GSH). Disulfides are stable at physiological pH but release the drug in the reducing environment of the cytosol.
What is the target of the Mirvetuximab antibody?

A: Mirvetuximab targets FOLR1 (Folate Receptor Alpha). This protein binds folic acid and its reduced derivatives and transports 5-methyltetrahydrofolate into cells. It is a member of the folate receptor family and can be anchored to membranes or exist in soluble form.

View the frequently asked questions answered by Creative Biolabs Support.

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Datasheet

Datasheet - ADC-L018.pdf

MSDS

MSDS - ADC-L018.pdf

COA

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