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The type of linker, cleavable or noncleavable, lends specific properties to the cytotoxic drug. For example, a non-cleavable linker keeps the drug within the cell. As a result, the entire antibody, linker and cytotoxic (anti-cancer) agent enter the targeted cancer cell where the antibody is degraded into an amino acid.
Bi-specific T-cell engager (BiTE) is a class of artificial bispecific monoclonal antibodies that are investigated for use as anti-cancer drugs. They direct a host's immune system, more specifically the T cells ' cytotoxic activity, against cancer cells.
Brentuximab vedotin [6] consists of the chimeric monoclonal antibody brentuximab (cAC10, which targets the cell-membrane protein CD30) linked with maleimide attachment groups, cathepsin-cleavable linkers (valine-citrulline), and para-aminobenzylcarbamate spacers to three to five units of the antimitotic agent monomethyl auristatin E (MMAE, reflected by the 'vedotin' in the drug's name). [7]
It includes the same linker, called "AcBut", and toxin, as gemtuzumab ozogamicin, which arose from the same collaboration. [12] The linker is a carbonyl-containing carboxylic acid. [ 13 ] The antibody, originally called G5/44, was created by grafting the complementarity-determining regions and some framework residues from the murine anti-CD22 ...
The binding of ligands to G-quadruplexes is vital for anti-cancer pursuits because G-quadruplexes are found typically at translocation hot spots. MM41, a ligand that binds selectively for a quadruplex on the BCL-2 promoter, is shaped with a central core and 4 side chains branching sterically out.
Mechanism of action of gemtuzumab ozogamicin. Gemtuzumab ozogamicin is a recombinant, humanized anti-CD33 monoclonal antibody (IgG4 κ antibody hP67.6) covalently attached to the cytotoxic antitumor antibiotic calicheamicin (N-acetyl-γ-calicheamicin) payload via a bifunctional linker (4-(4-acetylphenoxy)butanoic acid).
Monomethyl auristatin E is an antimitotic agent which inhibits cell division by blocking the polymerisation of tubulin.The linker to the monoclonal antibody is stable in extracellular fluid, but is cleaved by cathepsin once the conjugate has entered a tumor cell, thus activating the antimitotic mechanism.
Brentuximab vedotin (trade name: Adcetris) is a CD30 targeted antibody-drug conjugate (ADC), i.e. a monoclonal antibody chemically linked to a drug, and is constructed by chimeric anit-CD30 IgG1 antibody (cAC10), monomethyl auristatin E (MMAE, a potent cytotoxic drug) and a linker that attaches MMAE covalently to cAC10. [21]
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